Azathioprine versus sulfasalazine in maintenance of remission in severe ulcerative colitis. The beneficial effect of azathioprine on maintenance of remission in severe ulcerative colitis. Role of azathioprine in severe ulcerative colitis: one-year, placebo-controlled, randomized trial. Randomised controlled trial of azathioprine withdrawal in ulcerative colitis. Safety and efficacy of controlled-release mesalamine for maintenance of remission in ulcerative colitis. Pentasa UC Maintenance Study Group. Is maintenance therapy always necessary for patients with ulcerative colitis in remission? An oral preparation of mesalamine as long-term maintenance therapy for ulcerative colitis. A randomized, placebo-controlled trial. The Mesalamine Study Group. Clinical trial: once-daily mesalamine granules for maintenance of remission of ulcerative colitis - a 6-month placebo-controlled trial. Azathioprine in ulcerative colitis: final report on controlled therapeutic trial.
Azathioprine is useful as a steroid-sparing drug in patients with ulcerative colitis. Its role as monotherapy in the maintenance of disease remission has not been evaluated.
                In this prospective, randomized, open-label study, 25 patients with severe ulcerative colitis received either azathioprine (2.5 mg/Kg/day; Group A, n = 12) or sulfasalazine (6 g/day; Group B, n = 13). All patients received oral corticosteroids in a tapering dosage schedule initially. Treatment failure was defined as either disease relapse or drug withdrawal because of adverse effects.
                Five of 12 patients in Group A and 8 of 13 patients in Group B had sustained remission during the stipulated study period of 18 months (p = ns). Two patients in Group A had to stop azathioprine because of adverse effects (bone marrow suppression and acute pancreatitis). In Group A, all patients who had treatment failure developed it in the first half of the study while in Group B treatment failure occurred in both halves.
                The relapse rate of ulcerative colitis on maintenance therapy with azathioprine or sulfasalazine is comparable; there was a trend towards earlier treatment failure with azathioprine. The search is on to find more effective drug regimens for patients with severe ulcerative colitis, as conventional drugs such as sulfasalazine and its congeners fail to prevent relapse in a significant number of patients. Azathioprine has also been reported to be useful as a steroid-sparing drug in patients who suffer from frequent relapses. As these drugs when used individually fail to sustain remission in a significant number of patients, we evaluated the combination of these two drugs.
                Thirty-five newly diagnosed patients with severe ulcerative colitis were randomized into two groups; group A (combination therapy) received sulfasalazine and azathioprine, while group B (sulfasalazine monotherapy) received sulfasalazine and placebo. In addition, all the patients received steroids initially to achieve clinical remission. The patients were followed-up for a period of 1 year. The therapeutic outcome was measured by the number of patients who suffered relapse in each group.
                All the patients completed the 1-year study period. While 4 patients (23.5%) in group A suffered relapse of disease, 10 (55.6%) in group B suffered relapse, the difference being statistically significant. The relapse-free period was also significantly longer in group A.
                Combination therapy (sulfasalazine and azathioprine) is more effective than sulfasalazine and placebo in the maintenance of remission in patients with severe ulcerative colitis. To investigate the efficacy of azathioprine in treating patients with severe ulcerative colitis.
                One-year, randomized, placebo-controlled trial.
                83 patients with severe ulcerative colitis were enrolled. Fifty patients who relapsed within two months on corticosteroid withdrawal were randomized into two groups. The azathioprine group received oral sulfasalazine (6-8 g/day), oral prednisolone (1 mg/Kg/day) and oral azathioprine (2 mg/Kg/day). The placebo group received oral sulfasalazine (6-8 g/day), oral prednisolone (1 mg/Kg/day) and placebo. Corticosteroids were tapered over 12-16 weeks.
                Five patients (2 in azathioprine group, 3 in placebo group) dropped out of the study. Three patients in the azathioprine group had side effects. The number of patients going into complete remission and partial remission was not significantly different in the two groups. The proportion of relapses in the azathioprine group was lower than in the placebo group (p < 0.05).
                In patients with ulcerative colitis, azathioprine had no effect in achieving remission, when given in combination with prednisolone; however, it lowers the proportion of relapses. Side effects like pancreatitis and hepatitis are mild and respond promptly to drug withdrawal. To determine whether azathioprine can prevent relapse in ulcerative colitis.
                One year placebo controlled double blind trial of withdrawal or continuation of azathioprine.
                Outpatient clinics of five hospitals.
                79 patients with ulcerative colitis who had been taking azathioprine for six months or more. Patients in full remission for two months or more (67), and patients with chronic low grade or corticosteroid dependent disease (12) were randomised separately. 33 patients in remission received azathioprine and 34 placebo; five patients with chronic stable disease received azathioprine and seven placebo.
                Rate of relapse. Relapse was defined as worsening of symptoms or sigmoidoscopic appearance.
                For the remission group the one year rate of relapse was 36% (12/33) for patients continuing azathioprine and 59% (20/34) for those taking placebo (hazard rate ratio 0.5, 95% confidence interval 0.25 to 1.0). For the subgroup of 54 patients in long term remission (greater than six months before entry to trial) benefit was still evident, with a 31% (8/26) rate of relapse with azathioprine and 61% (17/28) with placebo (p less than 0.01). For the small group of patients with chronic stable colitis (six were corticosteroid dependent and six had low grade symptoms) no benefit was found from continued azathioprine therapy. Adverse events were minimal.
                Azathioprine maintenance treatment in ulcerative colitis is beneficial for at least two years if patients have achieved remission while taking the drug. Demonstration of the relapse preventing properties of azathioprine has implications for a large number of patients with troublesome ulcerative colitis, who may benefit from treatment with azathioprine. This 12-month, double-blind, placebo-controlled study randomized 205 ulcerative colitis patients in remission to placebo or controlled-release mesalamine at 4 g/day for 12 months. Patients were stratified to either pancolitis or left-sided disease, based on previous diagnosis. Maintenance of remission was defined as a sigmoidoscopic index of < 5, less than five stools per day, and the absence of rectal bleeding. A significantly greater number of patients maintained remission on mesalamine 4 g/day than on placebo at each of five study visits, following the first one-month visit (P < 0.05). The estimated 12-month remission rates for the mesalamine group were 64% (38% for placebo, P = 0.0004). Baseline subgroups (disease location, time since last flare of active disease, and previous response to oral/rectal steroids or sulfasalazine) did not influence remission rates. Treatment-related adverse events were rare. Controlled-release mesalamine is a safe and efficacious single agent for maintaining remission of ulcerative colitis. The efficacy of sulphasalazine and mesalazine in preventing relapse in patients with ulcerative colitis is well known. It is less clear how long such maintenance should be continued, and if the duration of disease remission is a factor that affects the risk of recurrence.
                To determine whether the duration of disease remission affects the relapse rate, by comparing the efficacy of a delayed-release mesalazine (Asacol, Bracco S.p.A., Milan, Italy) against placebo in patients with ulcerative colitis with short- and long-duration of disease remission.
                112 patients (66 male, 46 female, mean age 35 years), with intermittent chronic ulcerative colitis in clinical, endoscopic and histological remission with sulphasalazine or mesalazine for at least 1 year, were included in the study. Assuming that a lower duration of remission might be associated with a higher relapse rate, the patients were stratified according to the length of their disease remission, prior to randomization into Group A (Asacol 26, placebo 35) in remission from 1 to 2 years, or Group B (Asacol 28, placebo 23) in remission for over 2 years, median 4 years. Patients were treated daily with oral Asacol 1.2 g vs. placebo, for a follow-up period of 1 year.
                We employed an intention-to-treat analysis. In Group A, whilst no difference was found between the two treatments after 6 months, mesalazine was significantly more effective than placebo in preventing relapse at 12 months [Asacol 6/26 (23%), placebo 17/35 (49%), P = 0.035, 95% Cl: 48-2.3%]. In contrast, in Group B no statistically significant difference was observed between the two treatments, either at 6 or 12 months [Asacol 5/28 (18%), placebo 6/23 (26%), P = 0.35, 95% Cl: 31-14%] of follow-up. Patients in group B were older, and had the disease and remission duration for longer, than those in Group A.
                Mesalazine prophylaxis is necessary for the prevention of relapse by patients with ulcerative colitis in remission for less than 2 years, but this study casts doubt over whether continuous maintenance treatment is necessary in patients with prolonged clinical, endoscopic and histological remission, who are at very low risk of relapse. To compare the safety and efficacy of a pH-sensitive, polymer-coated oral formulation of mesalamine (Asacol, Procter & Gamble Pharmaceuticals, Cincinnati, Ohio) with those of placebo in maintaining remission in patients with ulcerative colitis.
                Multicenter, double-blind, placebo-controlled, randomized clinical trial.
                Eight private practices, five university-based medical centers, and four hospitals or clinics.
                264 patients with ulcerative colitis that had been maintained in remission for at least 1 month while the patients were receiving stable doses of sulfasalazine or any oral mesalamine product.
                Coated mesalamine at oral dosages of 0.8 g/d or 1.6 g/d or matching placebo for 6 months.
                Treatment success, defined as maintenance of remission after 6 months, and treatment failure, defined as relapse during the study (as indicated by proctosigmoidoscopy at 1, 3, or 6 months of treatment) or withdrawal due to adverse events. Safety was assessed on the basis of laboratory analyses and patient- and investigator-noted adverse events.
                189 patients were compliant with the protocol for 6 months or stopped receiving therapy because of relapse or adverse events. Of these 189 patients, 25 of the 63 patients (39.7%) in the placebo group had treatment success compared with 40 of the 68 patients (58.8% [95% CI, 46.4% to 71.3%]) in the group receiving mesalamine, 0.8 g/d (P = 0.036) and 38 of the 58 patients (65.5% [CI, 52.4% to 78.6%]) in the group receiving mesalamine, 1.6 g/d (P = 0.006). In the intention-to-treat analysis of all patients, 42 of the 87 patients (48.3%) in the placebo group had treatment success compared with 57 of the 90 patients (63.3% [CI, 52.8% to 73.8%]) in the group receiving mesalamine, 0.8 g/d (P = 0.050) and 61 of the 87 patients (70.1% [CI, 59.9% to 80.3%]) in the group receiving mesalamine, 1.6 g/d (P = 0.005). Age, sex, and race were not found to predict treatment success or failure. The mesalamine tablet was well tolerated, and no clinically significant changes were seen in hematologic, hepatic, or renal laboratory profiles.
                Coated mesalamine at oral dosages of 0.8 g/d and 1.6 g/d is safe and effective in maintaining remission in patients with quiescent ulcerative colitis. Ulcerative colitis (UC) is a chronic relapsing and remitting idiopathic inflammatory bowel disorder.
                To evaluate once-daily mesalamine (mesalazine) granules (MG) for maintenance of remission of UC.
                Randomized, double-blind, placebo-controlled trial of patients (n=209 MG, n=96 placebo) with UC in remission [revised Sutherland Disease Activity Index (SDAI) rectal bleeding=0, mucosal appearance <2] who took MG 1.5 g or placebo once-daily for up to 6 months. Primary efficacy endpoint: the percentage of patients who remained relapse-free at month 6/end of treatment. Relapse was defined as SDAI rectal bleeding score ≥1 and a mucosal appearance score ≥2, a UC flare, or initiation of medication to treat a UC flare.
                The percentage of relapse-free patients at month 6/end of treatment was higher with MG than placebo (78.9% vs. 58.3%, P < 0.001) in the intent-to-treat analysis. Significant differences (P ≤ 0.025) favouring MG were observed for most secondary endpoints including improvement in rectal bleeding, physician's disease activity rating, stool frequency, the SDAI at month 6/end of treatment, patients classified as a treatment success and relapse-free duration. The incidence of adverse events was similar between groups.
                Once-daily mesalamine (mesalazine) was effective in maintaining remission of UC for 6 months.
                © 2010 Salix Pharmaceuticals. Eighty patients, all of whom were suffering from a frank clinical attack of ulcerative colitis, were admitted to the trial. The attack was treated with a standard course of corticosteroids and the patients were immediately placed on treatment with either azathioprine in a dose of 2.5 mg/kg body weight or dummy tablets. The trial tablets were continued for one year while the patients were maintained under regular clinical, sigmoidoscopic, histological, haematological, and biochemical surveillance. If a patient relapsed during such maintenance treatment he or she was treated with a further course of corticosteroids without interrupting maintenance treatment.In the treatment of an actual attack of ulcerative colitis the results in the attacks which brought the 80 patients into the trial show that no benefit came from the addition of azathioprine to a standard course of corticosteroid therapy.Patients admitted in their first attack of ulcerative colitis showed no benefit from the one-year maintenance treatment with azathioprine, the benefits of which were confined to patients admitted in a relapse of established disease. Even in these the difference between the treated group and the control group failed to reach statistical significance, but the difference was big enough to suggest that there is a prima facie case for regarding azathioprine as of some benefit in this group of patients.
Azathioprine therapy appears to be more effective than placebo for maintenance of remission in ulcerative colitis. Azathioprine or 6-mercaptopurine may be effective as maintenance therapy for patients who have failed or cannot tolerate mesalazine or sulfasalazine and for patients who require repeated courses of steroids. More research is needed to evaluate superiority over standard maintenance therapy, especially in the light of a potential for adverse events from azathioprine. This review updates the existing review of azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis which was published in the Cochrane Library (Issue 1, 2007).