Medical management of left-sided ulcerative colitis and ulcerative proctitis: critical evaluation of therapeutic trials

BACKGROUND: The goal of this work was to critically evaluate the published studies on the treatment of ulcerative proctitis (UP) and left-sided ulcerative colitis (L-UC). The results of this review provided the content for the accompanying treatment guidelines, Clinical Guidelines for the Medical Management of Left-sided Ulcerative Colitis and Ulcerative Proctitis: Summary Statement. METHODS: All English language articles published between 1995 and September 2005 were identified through a comprehensive literature search using OVID and PubMed. The quality of the data supporting or rejecting the use of specific therapies was categorized by a data quality grading scale. An "A+" grade was assigned to treatment supported by multiple high-quality randomized controlled trials with consistent results, whereas a "D" grade was given to therapy supported only by expert opinion. The therapeutic efficacy of a treatment was defined by its success in treating UP and L-UC compared with placebo. A medication was ranked as "excellent" if it was specifically studied for UP and L-UC and had consistently positive results compared with placebo or another agent. Quality and efficacy scores were agreed on by author consensus. RESULTS: For the acute treatment of UP or L-UC, the rectally administered corticosteroids and mesalazine (5-ASA), either alone or in combination with oral 5-ASAs, are the most effective therapy: evidence quality, A+; efficacy, excellent. Only rectally administered 5-ASA received an A+/excellent rating for maintenance of remission. Infliximab received an A+ grade for induction and maintenance of remission but only a "good" rating because the studies were performed in all UC, not specifically UP or L-UC. CONCLUSIONS: This critical evaluation of treatment provides a "report card" on medications available for the management of patients with UP and L-UC. The guidelines should provide a useful reference and supplement for physicians treating UC patients.     

Exacerbation of chronic ulcerative colitis with mesalamine

Activation of ulcerative colitis with mesalamine has rarely been reported. In case 1, a 34-year-old man was treated with oral mesalamine, resulting in an exacerbation of colitis that rapidly improved with glucocorticoids and mesalamine withdrawal. Oral cromolyn sodium and occasional low-dose prednisone therapy has maintained long-term remission. In case 2, a 28-year-old man receiving prednisone treatment developed chest pain and myalgias 1 week after initiation of mesalamine that resolved on mesalamine withdrawal. A lower dose of mesalamine with continued glucocorticoids resulted in clinical improvement, and both drugs were tapered. Mesalamine sensitivity was documented endoscopically and histologically by evaluating mucosal changes after two mesalamine enemas during a 24-hour period. There was dramatic progression from quiescent disease to active colitis in 24 hours. Mesalamine sensitivity must be included in the differential diagnosis of ulcerative colitis exacerbations. Concurrent steroid therapy can suppress systemic side effects, making the diagnosis even more elusive.     

Maintenance Oral Sulfasalazine Prolongs Remission in Ulcerative Proctitis and Proctosigmoiditis

We have retrospectively compared the effectiveness of five different regimens for inducing and maintaining clinical remission in 206 patients with idiopathic proctitis (n = 115) and proctosigmoiditis (n = 91). The five therapeutic regimens were: corticosteroid enemas, 5-aminosalicylic acid (5-ASA) enemas, oral 5-ASA (sulfasalazine or mesalamine), corticosteroid enemas plus oral 5-ASA, or 5-ASA enemas plus oral 5-ASA. Clinical remission was achieved within 28 days of therapy in 47%, and eventually in 94% of these patients. No significant differences in efficacy were found among the five regimens. Most patients ultimately experienced a recurrence of symptoms, but the duration of remission was significantly longer with maintenance oral sulfasalazine or mesalamine (17.2 months) than with no therapy (11.8 months), P less than 0.01. We conclude that several regimens are equally effective in inducing remission of proctitis and proctosigmoiditis, although prolonged therapy may be needed to accomplish this goal. Maintenance oral 5-ASA significantly prolongs symptomatic remission in proctitis and proctosigmoiditis.     

Distal ulcerative colitis refractory to rectal mesalamine: role of transdermal nicotine versus oral mesalamine.

BACKGROUND: Distal ulcerative colitis usually responds to treatment with rectal mesalamine, but the management of refractory cases is poorly defined. AIM: To evaluate the possible therapeutic benefit of transdermal nicotine versus oral mesalamine. PATIENTS AND METHODS: Thirty patients with left-sided ulcerative colitis unresponsive to treatment with a mesalamine 4 g enema at bedtime were randomly allocated to additional therapy with either transdermal nicotine 15 mg daily or oral mesalamine 800 mg tid for four weeks. Clinical remission was evaluated by Rachmilewitz's activity index and confirmed by sigmoidoscopy. RESULTS: Remission was observed in 12 of 15 patients receiving additional treatment with nicotine and in five of 15 patients receiving additional treatment with oral mesalamine (P=0.027). CONCLUSIONS: The addition of transdermal nicotine to treatment with mesalamine enemas is significantly superior to combined therapy with oral and rectal mesalamine in patients with distal ulcerative colitis refractory to rectal mesalamine alone.     

Treatment of ulcerative colitis with oral mesalamine: advances in drug formulation, efficacy expectations and dose response, compliance, and chemoprevention

Sulfasalazine, olsalazine, balsalazide, delayed-release mesalamine, controlled-release mesalamine, mesalamine pellets, and Multi-Matrix System mesalamine are effective first-line therapies for the treatment of mildly to moderately active ulcerative colitis and for subsequent maintenance of remission. For induction therapy it is unclear if there is a dose response above 1.5 g, and for maintenance therapy existing data do not support a dose response above 1.5 g. Sulfasalazine has more frequent side effects than olsalazine, balsalazide, and mesalamine formulations. Once-daily dosing with multi-matrix system mesalamine 1.2 g tablets may lead to optimal compliance. Mesalamine >/= 1.2 g and sulfasalazine >/= 2 g reduce the risk of colorectal cancer in patients with ulcerative colitis. Drug formulations, efficacy expectations and dose response, toxicity expectations, compliance considerations, and chemoprevention considerations are reviewed.     

Long-term use of mesalamine enemas to induce remission in ulcerative colitis

The courses of 90 patients with left-sided ulcerative colitis that was unresponsive or intolerant to conventional therapy were retrospectively reviewed. They had been treated with 5-aminosalicylic acid enemas (mesalamine) on a long-term basis. After an initial 12-week course of treatment, 87% of the patients had improved by at least one grade of inflammation (improvement), and 54% of these were asymptomatic with normal colonic mucosa (remission). Overall, there was an 80% remission rate by 34 weeks. Remission rate was not affected by extent of sigmoid or left-sided colon disease before treatment or prior medication use for ulcerative colitis. Treatment with mesalamine enemas allowed patients to decrease or discontinue glucocorticoid treatment. Patients treated for relapse episodes responded as well as they did to the first course of treatment, whether the relapse occurred after discontinuation of mesalamine or during a tapering of the dose. In conclusion, extending mesalamine treatment to at least 34 weeks was beneficial in inducing a complete remission in 80% of patients unresponsive to conventional therapy.     

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.     

Placebo controlled evaluation of Xilei San,a herbal preparation in patients with intractable ulcerative proctitis

Background and Aim: Topical mesalamine or corticosteroid has shown efficacy in patients with ulcerative proctitis, but patients often become refractory to these interventions. Xilei San is a herbal preparation with evidence of anti‐inflammatory effects. We evaluated the efficacy of topical Xilei San in ulcerative proctitis patients. Methods: In a double blind setting, 30 patients with intractable ulcerative proctitis despite ≥ 4 weeks of topical mesalamine or corticosteroid were randomly assigned to True (n = 15) and placebo (n = 15). Patients in True received suppository Xilei San (0.1 g/dose per day of Xilei San), the other 15 received placebo suppository. The initial efficacy was evaluated on day 14. Primary endpoint of the trial was avoiding relapse during 180 days, relapse meant recurrence of active disease. Riley's index was applied for endoscopic and histological evaluations, while patients' quality of life was evaluated by an inflammatory bowel disease questionnaire. Results: On day 14, the number of patients who achieved remission, clinical activity index ≤ 4 in True was significantly higher versus placebo (P < 0.04). Likewise, at day 180, an 81.8% of patients in True were without relapse versus 16.7% in placebo (P < 0.001). Further, significant endoscopic (P < 0.01), histological (P < 0.02) and inflammatory bowel disease questionnaire (P < 0.04) improvements were observed in True, but not in placebo. Conclusions: This is the first controlled investigation showing significant clinical and endoscopic efficacy for Xilei San in patients with intractable ulcerative proctitis. Topical Xilei San was well tolerated, and was without safety concerns.     

Long-term use of mesalamine (Rowasa) suppositories in remission maintenance of ulcerative proctitis

OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of a single nightly 500-mg Rowasa (mesalamine) suppository as maintenance therapy for patients with ulcerative proctitis in remission. METHODS: In this 24-month, multicenter, double-blind trial, 65 patients with ulcerative proctitis in clinical and endoscopic remission were randomized to receive either a single nightly 500-mg rectal mesalamine (Rowasa) suppository or matching placebo as sole therapy. Efficacy was assessed by time to relapse (defined as rectal bleeding or increase in stool frequency for > or =1 wk and active inflammation upon endoscopy). RESULTS: Mean time to relapse was 453.4 days for mesalamine-treated patients and 158.0 days for placebo-treated patients. Survival analysis demonstrated that time to relapse was significantly greater for mesalamine-treated patients than for placebo-treated patients (p < 0.001). In addition, at both 12 and 24 months, the proportion of placebo-treated patients (86% at 12 months and 89% at 24 months) who relapsed was significantly (p < or = 0.001) greater than mesalamine-treated patients (32% and 46%, respectively). No statistically significant differences occurred between treatment groups in the reporting of any particular adverse event or the number of patients reporting adverse events. CONCLUSIONS: The results demonstrate that mesalamine suppositories are efficacious, well tolerated, and safe for the long-term maintenance of remission of ulcerative proctitis.     

Mesalamine in the treatment of mild to moderate active Crohn's ileitis: results of a randomized, multicenter trial

BACKGROUND & AIMS: The efficacy of 5-aminosalicylic acid (mesalamine) in the treatment of flare-ups of Crohn's disease is controversial. In previous studies, different locations and pathological behavior of Crohn's disease could have obscured the efficacy of these drugs that deliver their substance in different intestinal sites. The present study tested two different mesalamine formulations with 6-methylprednisolone in mild to moderate active Crohn's ileitis. METHODS: Ninety-four patients with Crohn's ileitis (Crohn's Disease Activity Index [CDAI], 180-350) were randomly assigned to receive for 12 weeks mesalamine tablets, 4 g (35 patients); mesalamine microgranular preparation, 4 g (28 patients); and 6-methylprednisolone, 40 mg (31 patients). Mesalamine microgranular preparation was a gelatin capsule containing 400 mg of mesalamine microgranules coated with Eudragit S, which has been shown to deliver the drug in the terminal ileum. RESULTS: Patients taking mesalamine tablets experienced a decrease of CDAI median score value of 113.5 (95% confidence interval [CI], 33-149) compared with 123 (95% CI, 77-155) in the mesalamine microgranular group and 154 (95% CI, 99-197) in the 6-methylprednisolone group (P = 0.07 [NS]). Remission at the final visit occurred in 19 of 31 (61%) patients taking steroids compared with 21 of 35 (60%) patients taking mesalamine tablets and 22 of 28 (79%) patients taking microgranular mesalamine (NS). Five patients on steroids were withdrawn because of side effects, and a case of pancreatitis was related to microgranular mesalamine. CONCLUSIONS: Mesalamine in microgranular formulation seems to be equally as effective as a standard dosage of steroids in the treatment of the mild to moderate form of Crohn's ileitis.     

Topical agents for idiopathic distal colitis and proctitis

Rectally administered topical agents have demonstrated efficacy in the maintenance of distal colitis (DC) and proctitis and as they are rarely associated with significant blood drug levels, side effects are infrequent. The topical 5-aminosalicylic acid (5-ASA) suppositories and enemas target different regions of the distal colon and are effective for proctitis and DC, respectively. They demonstrate clinical results that are better than oral 5-ASAs and are preferred to topical steroids with better clinical, endoscopic and histological outcomes, without the risk of adrenal suppression. Disease resistant to topical agents, however, can be extremely difficult to manage. The addition of oral 5ASAs, steroids, immunosuppressants and the anti-tumor necrosis factor-α agents may be effective, but can result in significant side effects and not all patients will respond to the therapies. It is for these patients that new and novel therapies are required. Novel topical agents have been proposed for the management of resistant DC. These agents included butyrate, cyclosporine, and nicotine enemas, as well as tacrolimus suppositories, and tacrolimus, ecabet sodium, arsenic, lidocaine, bismuth, rebamipide and thromboxane enemas. While some of these agents appear to demonstrate impressive outcomes, the majority have only been examined in small open-labeled studies. There is thus a desperate need for more randomized double-blinded placebo controlled studies to investigate the clinical utility of these topical therapies. This review summarizes the efficacy of the established topical therapies, and explores the available data on the new and novel topical agents for the management of DC and proctitis.     

Mesalamine induced symptom exacerbation of ulcerative colitis: Case report and brief discussion

This paper describes a rare case in which the oral administration of mesalamine resulted in the exacerbation of ulcerative colitis (UC) in a patient who was previously responsive to mesalamine and whose colitis had been in remission for eight years. Mesalamine and other 5-aminosalicylic acid compounds are the mainstay of treatment for UC; however up to 8% of patients are unable to take the medications due to intolerance or hypersensitivity reactions. Common drug reactions are fever, nausea, diarrhea and abdominal pain; however, exacerbation of UC has rarely been reported. This study highlights the importance of ruling out mesalamine as the causative agent in cases of UC exacerbations.     

A randomized trial of nicotine enemas for active ulcerative colitis.

BACKGROUND & AIMS: Ulcerative colitis (UC) is largely a disease of nonsmokers in which transdermal nicotine improves the symptoms but often causes adverse events (AEs). Nicotine enemas cause fewer AEs and were used as supplemental treatment for active UC. METHODS: We treated 104 patients with active UC with either 6-mg nicotine enemas or placebo enemas for 6 weeks in a randomized double-blind study. Patients continued their oral therapy, if any, for UC: 68 patients were taking mesalamine, 15 patients were taking prednisolone, and 12 patients were taking thiopurines during the study. Clinical, sigmoidoscopic, and histologic assessments were made at baseline and at the end of the study and symptoms were recorded daily on a diary card. The primary end point was induction of clinical remission and clinical improvement also was measured by the UC disease activity index. After the study, patients then used nicotine enemas daily for 4 weeks and sigmoidoscopy with a biopsy examination was repeated. AEs and salivary cotinine levels were monitored throughout the study. RESULTS: Clinical remission was achieved in 14 of 52 (27%) patients on active treatment and 14 of 43 (33%) patients on placebo (P = .55). The UC disease activity index improved by 1.45 points in the active group and by 1.65 points for those on placebo (P = .88). Only 1 patient discontinued treatment because of an AE (abdominal pain). In the 47 patients taking mesalamine only, active treatment conferred benefit that was not statistically significant; disease remission occurred in 9 of 25 patients on active therapy and 4 of 21 patients on placebo (P = .20). CONCLUSIONS: Six-milligram nicotine enemas were well tolerated but were not found to be efficacious for active UC.     

Mesalamine with MMX™ technology for the treatment of ulcerative colitis

Mesalamine with MMX Multi Matrix System^® technology (hereafter referred to as MMX mesalamine) is an oral, high-strength (1.2 g/tablet), once-daily formulation of 5-aminosalicylic acid used for the treatment of ulcerative colitis. This new formulation has been designed to provide delayed and prolonged 5-aminosalicylic acid release throughout the colon. In recent clinical studies, MMX mesalamine (taken as a once-daily dose of 2.4 or 4.8 g) effectively induced clinical remission and mucosal healing versus placebo in patients with active, mild-to-moderate ulcerative colitis. Once remission was achieved, MMX mesalamine effectively maintained disease remission in the majority of patients for at least 12 months. In this paper, we comprehensively review the results of studies exploring the clinical pharmacology, efficacy and safety of MMX mesalamine in patients with ulcerative colitis, and examine the implications of these findings on clinical practice.     

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.     

Randomized clinical trial of Plantago ovata seeds (dietary fiber) as compared with mesalamine in maintaining remission in ulcerative colitis. Spanish Group for the Study of Crohn's Disease and Ulcerative Colitis (GETECCU)

OBJECTIVE: Butyrate enemas may be effective in the treatment of active distal ulcerative colitis. Because colonic fermentation of Plantago ovata seeds (dietary fiber) yields butyrate, the aim of this study was to assess the efficacy and safety of Plantago ovata seeds as compared with mesalamine in maintaining remission in ulcerative colitis. METHODS: An open label, parallel-group, multicenter, randomized clinical trial was conducted. A total of 105 patients with ulcerative colitis who were in remission were randomized into groups to receive oral treatment with Plantago ovata seeds (10 g b.i.d.), mesalamine (500 mg t.i.d.), and Plantago ovata seeds plus mesalamine at the same doses. The primary efficacy outcome was maintenance of remission for 12 months. RESULTS: Of the 105 patients, 102 were included in the final analysis. After 12 months, treatment failure rate was 40% (14 of 35 patients) in the Plantago ovata seed group, 35% (13 of 37) in the mesalamine group, and 30% (nine of 30) in the Plantago ovata plus mesalamine group. Probability of continued remission was similar (Mantel-Cox test, p = 0.67; intent-to-treat analysis). Therapy effects remained unchanged after adjusting for potential confounding variables with a Cox's proportional hazards survival analysis. Three patients were withdrawn because of the development of adverse events consisting of constipation and/or flatulence (Plantago ovata seed group = 1 and Plantago ovata seed plus mesalamine group = 2). A significant increase in fecal butyrate levels (p = 0.018) was observed after Plantago ovata seed administration. CONCLUSIONS: Plantago ovata seeds (dietary fiber) might be as effective as mesalamine to maintain remission in ulcerative colitis.     

Efficacy and safety of mesalamine 1 g HS versus 500 mg BID suppositories in mild to moderate ulcerative proctitis: a multicenter randomized study

BACKGROUND: Ulcerative proctitis (UP) usually presents as fresh rectal bleeding. Successful treatment using topical mesalamine 5-aminosalicyclic acid (5-ASA) 500 mg BID suppository led to developing a once-a-day formulation that could contribute to better acceptability and ease of use by patients. The objective of this randomized trial, conducted in 18 centers, was to compare efficacy of 2 modes of treatment with 5-ASA suppositories. METHODS: Ninety-nine patients with mild or moderate UP limited to 15 cm of the anal margin, evidenced by a disease activity index (DAI) between 4 and 11, were randomized to 5-ASA 500 mg suppository (Canasa; Axcan Pharma) BID or 1 g at bedtime (HS) for 6 weeks. The study used a noninferiority hypothesis based on the mean difference in DAI values after 6 weeks of treatment on an intent-to-treat basis using analysis of covariance. DAI was derived from a composite of the measures of stool frequency, rectal bleeding, mucosal visualization at endoscopy, and general well being. RESULTS: There was no difference between groups at baseline for demographic and clinical parameters. Mean DAIs fell from 6.6 +/- 1.5 (SD) to 1.6 +/- 2.3 in the 500 mg BID group (n = 48) and from 6.1 +/- 1.5 to 1.3 +/- 2.2 in the 1 g HS group (n = 39). There was no significant difference (P = 0.74) in mean DAI at week 6 between the 2 groups. Both groups showed a significant reduction (P < 0.0001) in DAI over the course of the 6 weeks. Both formulations showed effectiveness in reducing each individual component of the DAI. There was no significant difference between treatments in adverse events, and both groups had an overall drug compliance of greater than 95%. CONCLUSION: This study showed that 1 g HS and 500 mg BID mesalamine suppository treatments of UP patients were equivalent in all facets of efficacy, safety, and compliance in a 6-week trial.     

Intermittent therapy with high-dose 5-aminosalicylic acid enemas maintains remission in ulcerative proctitis and proctosigmoiditis

PURPOSE: The aim of this study was to compare the efficacy of intermittent therapy with mesalazine enemas and continuous oral mesalazine to maintain remission of distal ulcerative colitis or proctitis. METHODS: Thirt-yeight patients with distal ulcerative colitis (n=17) or ulcerative proctitis (n=21) in clinical, endoscopic, and histologic remission were randomly assigned to receive either oral mesalazine (0.5 g three times/day, Eudragit L coating, n=19) or intermittent therapy with mesalazine enemas (4 g of 5-aminosalicylic acid enema every third night, n=19). Both groups were comparable in regard to sex, age, age at disease onset, extent and duration of disease, number and mode of treatment of previous attacks, and time in remission. Patients were reviewed at the beginning of the study and, subsequently, at two-month intervals for 24 months or until a relapse occurred. At each visit, diaries were reviewed and clinical and laboratory assessments were performed. Sigmoidoscopy was carried out and biopsies were obtained by a blinded observer. Histology was assessed without knowledge of the patient's clinical state or treatment category. RESULTS: At the end of the study, 6 of 19 patients on oral mesalazine (32 percent) and 14 of 19 patients on mesalazine enemas (74 percent) were still in full remission (log rank test: 15.280,P <0.001). Differences in relapse rates between groups were significant even when data were stratified by extent of disease (P <0.01). In the oral group, six and seven patients relapsed at 12 and 24 months, respectively. In the enema group, three and two relapses occurred in the first and second year of the study, respectively. All patients complied with the treatment satisfactorily and there were no dropouts. CONCLUSION: These results suggest that intermittent therapy with mesalazine enemas is more effective than continuous oral mesalazine in maintaining remission in patients with distal ulcerative colitis and proctitis.Read at the meeting of the First United European Gastroenterology Week, Athens, Greece, September 25 to 30, 1992.     

Optimum dose of olsalazine for maintaining remission in ulcerative colitis.

To evaluate the optimum dose of olsalazine for maintaining remission in ulcerative colitis, 198 patients in remission for more than three months were randomly assigned to receive 0.5 g, 1.0 g, or 2.0 g/day for 12 months. A dose-ranging effect was detected in the per protocol analysis, with remission rates of 60% (0.5 g), 70% (1.0 g), and 78% (2.0 g) (p = 0.03, trend in proportions). The higher dose was most effective in patients with proctitis (90% remission on 2 g/day, p = 0.03) or those in remission for less than 12 months before the trial (88% remission on 2 g/day, p = 0.0006). There was little dose-ranging effect in patients with extensive colitis or those in remission for more than 12 months. Diarrhoea necessitated treatment withdrawal in 12%. The optimal dose of olsalazine for maintaining remission in ulcerative colitis is 1 g/day. For patients with proctitis or recent relapse, 2 g/day may be preferable, although the dose seems to be less important in patients with more extensive disease or those in long term remission.