Putting rectal 5-aminosalicylic acid in its place: the role in distal ulcerative colitis

Oral aminosalicylates such as sulfasalazine and mesalamine are widely prescribed for the treatment of mild or moderately active distal ulcerative colitis. However, a critical review of the literature demonstrates that rectal 5-aminosalicylic acid (5-ASA) is the optimal therapy for this disease. Meta-analyses of published trials show that rectally delivered 5-ASA is superior to placebo and to conventional rectal corticosteroids in inducing remission of distal ulcerative colitis, whereas the combination of rectal 5-ASA with a rectal corticosteroid or oral aminosalicylate is superior to rectal 5-ASA alone. For maintaining remission of distal ulcerative colitis, rectal 5-ASA is significantly better than placebo and at least as effective as oral 5-ASA. The dosage forms available for rectal delivery include suppositories, foams, and liquid enemas, and selection among these preparations should be guided by the proximal extent of disease and patient preference. The efficacy of rectal 5-ASA is complemented by its low rate of reported adverse effects, which may reflect its reduced potential for systemic absorption. This review summarizes the evidence supporting the role of rectal 5-ASA as a first-line therapy for mild or moderately active distal ulcerative colitis, and offers guidelines for its use.     

The role of aminosalicylates in the treatment of ulcerative colitis

Aminosalicylates (5-ASA, sulfasalazine and mesalazine) play a central role in the treatment of ulcerative colitis (UC). For acute treatment of mild to moderate flares and in maintenance treatment, their efficacy has been established. Since ulcerative colitis is limited to the distal colon in two thirds of the patients, topical therapy also plays an important role. In mild/moderate active disease 5-ASA 4 g/d is as effective as oral corticosteroids. Ulcerative proctitis is treated with 2 x 500 mg or 1 x 1 g suppositories and proctosigmoiditis with 1 to 4 g enemas. Oral 5-ASA is also safe in maintenance treatment and is generally well tolerated. The risk of colorectal tumours is increased in patients with longstanding ulcerative colitis and epidemiological evidence indicates that chronic 5-ASA treatment reduces this risk. However, at present there is insufficient evidence to maintain patients on life-long 5-ASA maintenance treatment for this indication.     

Drug therapy for ulcerative colitis

Ulcerative colitis (UC) is an inflammatory destructive disease of the large intestine occurred usually in the rectum and lower part of the colon as well as the entire colon. Drug therapy is not the only choice for UC treatment and medical management should be as a comprehensive whole.Azulfidine, Asacol, Pentasa, Dipentum, and Rowasa all contain 5-aminosalicylic acid (5-ASA), which is the topical anti-inflammatory ingredient. Pentasa is more commonly used in treating Crohn‘s ileitis because Pentasa capsules release more 5-ASA into the small intestine than Asacol tablets. Pentasa can also be used for treating mild to moderate UC. Rowasa enemas are safe and effective in treating ulcerative proctitis and proctosigmoiditis. The sulfafree 5-ASA agents (Asacol, Pentasa, Dipentum and Rowasa) have fewer side effects than sulfa-containing Azulfidine. In UC patients with moderate to severe disease and in patients who failed to respond to 5-ASA compounds,systemic (oral) corticosteroids should be used. Systemic corticosteroids (prednisone, prednisolone, cortisone, etc.)are potent and fast-acting drugs for treating UC, Crohn‘s ileitis and ileocolitis. Systemic corticosteroids are not effective in maintaining remission in patients with UC.Serious side effects can result from prolonged corticosteroid treatment. To minimize side effects, corticosteroids should be gradually reduced as soon as the disease remission is achieved. In patients with corticosteroid-dependent or unresponsive to corticosteroid treatment, surgery or immunomodulator is considered. Immunomodulators used for treating severe UC include azathioprine/6-MP,methotrexate, and cyclosporine. Integrated traditional Chinese and Western medicine is safe and effective in maintaining remission in patients with UC.     

Short-chain fatty acid enemas: A cost-effective alternative in the treatment of nonspecific proctosigmoiditis

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.b.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.Read at the meeting of The American Society of Colon and Rectal Surgeons, Boston, Massachusetts, May 12 to 17, 1991.     

Measurement of colonic mucosal concentrations of 5-aminosalicylic acid is useful for estimating its therapeutic efficacy in distal ulcerative colitis: comparison of orally administered mesalamine and sulfasalazine

OBJECTIVES: Oral 5-aminosalicylic acid (5-ASA) preparations have been used frequently in the treatment of ulcerative colitis. However, there have been few reports investigating the relationship between colonic mucosal concentrations of 5-ASA and its clinical efficacy when oral sulfasalazine or 5-ASA compounds were administered. The aim of this study is to compare the mucosal concentrations of 5-ASA ensured by sulfasalazine or mesalamine, and to define the clinical significance of the measurement of 5-ASA concentrations in the treatment of distal ulcerative colitis. MATERIALS AND METHODS: Biopsies were taken from the rectum and sigmoid colon of the oral sulfasalazine group (n = 13) and the slow-release 5-ASA (mesalamine) group with (n = 5) or without (n = 11) rectal administration of 5-ASA. High-pressure liquid chromatography was used to measure the tissue concentrations of 5-ASA and its metabolites. We compared the 5-ASA concentrations of the sulfasalazine group with the mesalamine group. Furthermore, we analyzed the relationship between tissue 5-ASA concentrations and the Disease Activity Index (DAI). RESULTS: The concentrations of 5-ASA and acetyl-5-ASA in the sulfasalazine group were higher than those in the group taking oral mesalamine alone (p < 0.01). The concentration of 5-ASA was much higher in the patients who received oral and rectal mesalamine in an enema than in the patients who had oral mesalamine alone. There was a significant inverse correlation between the DAI and concentrations of 5-ASA in the rectum (r = 0.712, p < 0.001). CONCLUSIONS: We demonstrated that the colonic mucosal concentration of 5-ASA was significantly higher in the sulfasalazine group than in the mesalamine group. Furthermore, the concentrations of mucosal 5-ASA may be a good marker for the estimation of its efficacy in the treatment of ulcerative colitis.     

A meta-analysis and overview of the literature on treatment options for left-sided ulcerative colitis and ulcerative proctitis

OBJECTIVES: Therapeutic trials in left-sided ulcerative colitis (L-UC) and ulcerative proctitis (UP) have lacked control for medication type, dose, delivery, and duration of therapy. METHODS: All published therapeutic articles and abstracts in L-UC or UP from 1958-1997 were reviewed. Improvement, remission rates, and adverse events were recorded for all (ALL), placebo-controlled (PC) studies, and for PC studies passing quality assessment (QA) scoring. Meta-analysis was used where appropriate. RESULTS: Left-sided UC: For active disease, 67 studies (17 PC; 10 QA) were identified. Mesalamine enemas achieved remission in a duration but not a dose response (QA), with higher remission rates than steroid enemas (ALL) and clinical improvement rates superior to oral therapies (QA, ALL). Remission maintenance: 17 (six PC, six QA) studies were identified. Mesalamine therapies had comparable remission rates at 6 months, with a possible dose but not delivery effect. Mesalamine enema dosing intervals between QHS to Q3 days maintained efficacy. Reported adverse events were most common with oral sulfasalazine and dose-independent for mesalamine. Withdrawals from therapy were less than placebo, or < or =3%. Ulcerative proctitis: For active disease, 18 (nine PC, three QA) studies were identified. Mesalamine suppositories achieved clinical improvement and remission in a duration but not dose response, with higher rates of remission than topical steroids (ALL). Remission maintenance: three (three PC, two QA) studies were identified. Remission ranged from 75% to 90% (6 months) and 61-90% (12 months) for mesalamine agents. Reported adverse events were most common for mesalamine foam (8%). Withdrawals from therapy were <2%. CONCLUSIONS: In L-UC and UP, the efficacy and side-effect profile of topical mesalamine are dose independent and superior to oral therapies and topical steroids. Economic analysis suggests that use of these agents will also result in an overall decrease in patient costs.     

Clinical guidelines for the medical management of left-sided ulcerative colitis and ulcerative proctitis: summary statement

There are few published guidelines for the treatment of inflammatory bowel disease. Physicians choose therapy based on evidence-based data, peer and expert opinion, and personal experience. This article provides treatment guidelines for the induction and maintenance of ulcerative proctitis and left-sided colitis and the management of disease refractory to 5-aminosalicylic acid (5-ASA) compounds and corticosteroids The guidelines are derived from evidence-based data and, when lacking, expert opinion or the authors' experience. The comprehensive review of the literature is presented in the accompanying article, "The Medical Management of Left-Sided Ulcerative Colitis and Ulcerative Proctitis: Critical Evaluation of Therapeutic Trials". Rectally administered 5-ASA and corticosteroid suppositories are effective treatment for most ulcerative proctitis patients. Corticosteroid and 5-ASA enemas, which reach the splenic flexure of the colon, are recommended for patients with left-sided ulcerative colitis. The combination of rectally administered 5-ASA enemas and oral 5-ASA agents may afford better treatment of left-sided colitis and possibly prevent proximal extension of disease. Patients refractory to 5-ASAs and corticosteroids may require an immunomodulator or biological response modifier therapy. Those who have ongoing signs and symptoms of ulcerative proctitis and left-sided ulcerative colitis despite maximal medical therapy require a proctocolectomy.     

Topical salicylate therapy (4-ASA and 5-ASA enemas)

Topical therapy with amino salicylate enemas is the treatment of choice for proctitis, proctosigmoiditis, and left-sided ulcerative colitis. Adjunctive sulfasalazine therapy is often required. Relapse rates of 80 per cent can be expected within 3 months of discontinuing therapy.     

Role of mesalazine in acute and long-term treatment of ulcerative colitis and its complications

BACKGROUND: Sulfasalazine, consisting of 5-aminosalicylic acid bound to sulfapyridine by a diazo bond, was first used for treatment of ulcerative colitis in the early 1940s and later found effective in placebo-controlled trials for acute disease and for long-term maintenance of remission. Later studies found that the active moiety is 5-ASA (mesalazine, mesalamine) and the sulfapyridine moiety acts as a carrier molecule but causes many of the symptomatic adverse reactions. METHODS: Review of the literature. RESULTS: The finding that 5-ASA in the active motility led to the development of mesalazine prodrugs, olsalazine (Dipentum) and balsalazide (Colazide, Colazal), and targeted release mesalazine preparations, such as Asacol, Pentasa, and Salofalk, as well as enemas and suppository preparations for distal disease. Most patients with adverse effects from sulfasalazine will tolerate mesalazine. Mesalazine has been shown equivalent or superior to sulfasalazine, and superior to placebo, with a dose-response benefit, in inducing remission of acute disease. and comparable to sulfasalazine and superior to placebo for long-term maintenance of remission. Better tolerance of mesalazine and the ability to use higher doses favor its use in patients intolerant of sulfasalazine and in patients failing to respond to usual doses of sulfasalazine. Adverse effects from mesalazine are uncommon, but include idiosyncratic worsening of the colitis symptoms and renal toxicity. Mesalazine is safe to use during pregnancy and for nursing mothers. As maintenance therapy, mesalazine may reduce the risk of developing colorectal carcinoma. CONCLUSION: Mesalazine represents effective and well-tolerated first-line therapy for mildly to moderately acute disease as well as for the long-term maintenance treatment in the patient with ulcerative colitis.     

Radiation-induced proctosigmoiditis

In a prospective study, 37 consecutive patients with radiation-induced proctosigmoiditis were randomized to receive a four-week course of either 3.0 g oral sulfasalazine plus 20 mg twice daily rectal prednisolone enemas (group I, N = 18) or 2.0 g twice daily rectal sucralfate enemas plus oral placebo (group II, N = 19). The two groups were comparable with respect to demographic features, duration of symptoms, and clinical and endoscopic staging of the disease. Fifteen patients in group I and 17 in group II completed the trial. At four weeks, both groups showed significant clinical improvement (P less than 0.01 for group I and P less than 0.001 for group II) and endoscopic healing (P less than 0.01 for group I and P less than 0.001 for group II). When the two groups were compared, sucralfate enemas showed a significantly better response as assessed clinically (P less than 0.05), although endoscopically the response was not statistically different (P greater than 0.05). We conclude that both treatment regimens are effective in the management of radiation proctitis. Sucralfate enemas give a better clinical response, are tolerated better, and because of the lower cost should be the preferred mode of short-term treatment.     

Topical therapy is underused in patients with ulcerative colitis

The availability of new topical preparations for the treatment of left sided ulcerative colitis offers a therapy optimization for many patients. Rectal application of steroids and 5-aminosalicylic acid (5-ASA) is associated with fewer side effects and has a higher therapeutic efficacy in left-sided colitis as compared to a systemic therapy. Therefore, we were interested in the use of topical therapy in patients with ulcerative colitis. The key question was whether topical treatment is more frequently used than oral therapy in patients with proctitis and left sided colitis. Data of 800 patients of the Swiss IBD cohort study were analyzed.Sixteen percent of patients of the cohort had proctitis, 21% proctosigmoiditis and 41% pancolitis. Topical therapy with 5-ASA or corticosteroids was given in 26% of patients with proctitis, a combined systemic and topical treatment was given in 13%, whereas systemic treatment with 5-ASA without topical treatment was given in 29%. Proportion of topical drug use decreased with respect to disease extension from 39% for proctitis to 13.1% for pancolitis (P = 0.001). Patients with severe colitis received a significantly higher dose of topical 5-ASA than patients in remission.Side effects of topical or systemic 5-ASA or budesonide treatment were less frequently seen compared to other medications. Topical treatment was frequently stopped over time. The quality of life was the same in patients with limited disease compared to patients with pancolitis.Topical treatment in proctitis patients was underused in Switzerland. Since topical treatment is safe and effective it should be used to a larger extend.     

Successful treatment for ulcerative proctitis with rectal tacrolimus in an 8-year-old girl with intolerance to mesalamine

Ulcerative colitis (UC) is defined as a chronic inflammatory condition causing continuous mucosal inflammation of the colon without granulomas on biopsy. It affects the rectum, and, to a variable extent, the colon in continuity and is characterized by a relapsing and remitting course. Oral 5-aminosalicylic acid (5-ASA) regimens are recommended as first-line induction therapy for mild to moderately active pediatric UC and for maintenance of remission regardless of other initial treatments. In large clinical trials in adults, mesalamine intolerance was found in 2–5 % of the patients. We present a case of an 8-year-old female patient with intolerance to mesalamine and proctitis resistant to conventional therapy who responded to rectal tacrolimus treatment. The patient started with a dose of 2 mg/day at night with an excellent response. She reported feeling better than any of the previously prescribed treatments and without feeling the discomfort of previously administered enemas. After four weeks of treatment, the dose was reduced to 2 mg/week with no relapses. Tacrolimus suppositories were very well tolerated, and no adverse effects have been reported. Although only very little data has been published, rectal tacrolimus seems to be safe and of efficacy in ulcerative proctitis resistant to standard therapy.     

5-Aminosalicylic Acid Enemas in Refractory Distal Ulcerative Colitis: A Randomized, Controlled Trial

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.     

The metabolism of mesalamine and its possible use in colonic diverticulitis as an anti-inflammatory agent

5-Aminosalicylic acid (5-ASA) is the mainstay of therapy for inflammatory bowel disease (IBD), particularly ulcerative colitis. 5-ASA is the active moiety in sulfasalazine, which was initially developed for the treatment of rheumatoid arthritis more than 60 years ago, by linking 5-ASA with sulfapyridine Because many of the side effects related to sulfasalazine were found to be due to sulfapyridine, several drugs that contain 5-ASA, and lack the side-effect profile of sulfasalazine, have been developed during the last 2 decades. These drugs have proven to be quite effective in treating mild-to-moderate symptoms of IBD, as well as inducing and maintaining remission. Although they exert anti-inflammatory effects, their exact mechanism of action remains elusive. Nonetheless, their success in treating IBD has led to studies using this class of drugs for novel indications. Several recent studies have evaluated the use of 5-ASA drugs (mesalamine) for the treatment of uncomplicated acute diverticulitis. In this review, we will briefly discuss the development of 5-ASA releasing drugs, their metabolism, side effects, indications, mechanisms of action, and the rationale for the clinical use of mesalamine in colonic diverticulitis.     

Initial therapy for mild to moderate Crohn's disease: mesalamine or budesonide?

The initial choice of therapy for mild to moderately active Crohn's disease is controversial. Both the National Cooperative Crohn's Disease Study (NCCDS) and the European Cooperative Crohn's Disease Study (ECCDS) demonstrated that sulfasalazine is effective for the induction of remission. Subsequent studies of new mesalamine formulations showed inconsistent results; two trials, however, demonstrated a statistically significant improvement with Pentasa and Asacol treatment, and meta-analyses suggest a modest benefit of mesalamine maintenance therapy. The NCCDS and ECCDS trials found that corticosteroid therapy is much more effective than sulfasalazine for induction of remission, but corticosteroids did not show maintenance benefits. Corticosteroid use is frequently associated with adverse effects, and the majority of patients treated with prednisone become either steroid-refractory or steroid-dependent; many of these patients ultimately need treatment with immunosuppressives and/or surgery. Budesonide, a topical corticosteroid with high first-pass hepatic metabolism, is slightly less effective in inducing remission than conventional corticosteroids but is significantly less likely to cause side effects. Budesonide 9 mg/day was shown to be more effective than mesalamine (Pentasa 4 g/day) for induction therapy, but budesonide has been ineffective as a maintenance therapy. Mesalamine may be useful for patients with more extensive disease, those intolerant of sulfasalazine, or those with contraindications or intolerance to budesonide. Alternatively, sulfasalazine is effective in the presence of colonic disease. Clinicians must decide on the basis of the existing evidence whether budesonide or mesalamine is the preferred initial therapy for active Crohn's disease.     

Effect of weekend 5-aminosalicylic acid (mesalazine) enema as maintenance therapy for ulcerative colitis: results from a randomized controlled study

BACKGROUND: 5-aminosalicylic acid (5-ASA) is known to be effective in the treatment of active ulcerative colitis (UC). The aim of the current study was to investigate the effect of 5-ASA enemas, as a maintenance therapy for UC, when administered twice weekly as a weekend treatment regimen, compared to daily oral 5-ASA alone. We hypothesized that the weekend enema therapy would be better tolerated by patients who worked or attended school. METHODS: Between January 2004 and August 2005, patients with UC, in whom remission of the condition had just been induced, were randomly assigned to either: the weekend 5-ASA enema group (n=11), who received 1 g 5-ASA enemas twice a week on Saturday and Sunday plus oral 5-ASA 3 g/day for 7 days, or to the daily oral 5-ASA use only group (n=13), who received only oral 5-ASA 3 g/day for 7 days. The primary endpoint of the study was defined as the incidence of relapse. The study was stopped after 24 patients had been enrolled because an interim analysis showed a significant benefit of the weekend 5-ASA enema group. RESULTS: In the weekend enema group, 2 patients (18.2%) had relapses compared with 10 (76.9%) in the oral 5-ASA only group. The multivariate hazard ratio of relapse associated with weekend 5-ASA enema, relative to the oral alone group, was 0.19 (95% confidence interval, 0.04-0.94). CONCLUSIONS: This study demonstrated the beneficial effects of adding weekend 1 g 5-ASA enema to daily 3 g oral 5-ASA as maintenance therapy for UC.     

Medical management of ulcerative proctitis, proctosigmoiditis, and left-sided colitis.

Ulcerative colitis distal to the splenic flexure includes disease confined to the rectum (proctitis), rectosigmoid (proctosigmoiditis or distal colitis), or extending to the descending colon or splenic flexure (left-sided colitis). These subtypes represent up to 60% to 80% of newly presenting cases of ulcerative colitis. Although these conditions are defined by the extent of colon that is affected, they also share the characteristic of being amenable to topical therapy. In general, the course of disease is milder and symptoms are less severe than in patients with more extensive colonic involvement. Nonetheless, symptoms may significantly impair patients' health-related quality of life. Treatment options include the oral and/or rectal 5-aminosalicylate (5-ASA) preparations. Rectal therapy delivering higher concentrations of active medication (5-ASA or glucocorticoids) directly to the inflamed mucosa while minimizing systemic absorption provides a highly effective and safe treatment. Oral glucocorticoids are indicated in patients who are resistant to or intolerant of 5-ASA therapy. Immunomodulators have an important role in individuals with glucocorticoid dependent or glucocorticoid refractory disease. This article reviews the clinical diagnosis and current medical management of ulcerative proctitis, proctosigmoiditis, and left-sided ulcerative colitis, including patients resistant to conventional medical therapy.     

A new oral delivery system for 5-ASA: preliminary clinical findings for MMx

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

5-Aminosalicylic Acid Suppositories in the Maintenance of Remission in Idiopathic Proctitis or Proctosigmoiditis: A Double-Blind Placebo-Controlled Clinical Trial

Thirty patients with distal ulcerative colitis in remission (17 proctitis, 13 proctosigmoiditis) were randomly given either 5-aminosalicylic acid (5-ASA) or placebo suppositories, 400 mg bid. During the 1-yr follow-up, patients were assessed clinically every month, and flexible sigmoidoscopy with a rectal pinch biopsy specimen and laboratory data were carried out every 3 months. Two patients in the 5-ASA group chose to withdraw from the study, one relapsed, and 12 remained in remission. In the placebo group, one patient chose to withdraw, 11 relapsed, and three remained in remission. The cumulative remission rate at the 12th month was 92% in the 5-ASA group and 21% in the placebo group. Log rank test showed a significant difference in the relapse rate between the two groups (chi 2 = 14.26, p less than 0.001). No side effects were observed. We conclude that 5-ASA in suppository form (800 mg/day), administered for 1 yr, is safe and effective in maintaining remission of distal ulcerative colitis.     

Failure of 5-Aminosalicylic acid enemas to improve chronic radiation proctitis

Radiation proctitis is a well-known complication of abdominal and pelvic radiation. Conventional medical and surgical treatment often is disappointing. 5-Aminosalicylic Acid (5-ASA)is the active component in sulfasalazine and is effective in the treatment of distal ulcerative colitis. Four patients with radiation proctitis were treated with 4 g 5-ASA by enema nightly for two to six months. Patients were seen monthly, interviewed, and a sigmoidoscopic exam performed. No change was seen in the degree of mucosal inflammation on follow-up sigmoidoscopic exams. Three patients noted no change in their symptoms of bleeding, pain, or tenesmus. One patient noted initial improvement, but this was not sustained. 5-ASA enemas do not appear to be effective in the treatment of radiation proctitis.