Maintenance Therapy In Ulcerative Colitis Research Articles

Crohn’s Disease: We are in it for the Long Haul

Crohn’s Disease: We are in it for the Long Haul

Clinical Update: Inflammatory Bowel Disease

Inflammatory bowel disease(IBD) which is well known as Crohn’s disease and ulcerative colitis is a chronic disorder that repeats improvement and exacerbation. The possible causes of the disease are environmental factors, genetic factors and immune deficiency resulted from bacterial infection. Recently, IL-23 is proved to be a main cytokine which has a central role in Crohn’s disease. The diagnosis of IBD is made by clinical manifestation, serologic test, endoscopic finding and histologic finding. The mainstay of remission and maintenance therapy of ulcerative colitis is 5-aminosalicylate(5-ASA). Steroid can be used in severe or refractory case and nowadays, budesonide shows a good effect with minimal side effects. In cases of steroid dependent, we can use the immunomodulators such as azathioprine, cyclosporin and 6-thioguanine. The cytokine associated with inflammation of IBD has been emphasized and the treatment which targets the cytokine such as tumor necrosis factor is tried. Infliximab and adalimumab block tumor necrosis factors-a and they are proved the efficacy by many clinical trial. Leukocytapheresis(LCAP) is tried in ulcerative colitis since 1980 in Japan. When we treat IBD patients, we need to consider all the things such as safety, side effects and economy of the patients. We expect that the development of new biologic agent which is more cost effective and more effect with more convinience.

Maintenance therapy for ulcerative colitis has no impact on changes in the extent of ulcerative colitis

Background and aimAlthough the efficacy of maintenance remission therapy in ulcerative colitis (UC) has been proved in many studies, little is known about its possible effect on the extent of the disease. The aim of the present multicenter Belgian study was to evaluate the potential role of UC maintenance therapy on the colonic extension of the disease. Materials and methodsA total of 98 patients, 56 males, 42 females, mean age 52 years, range 22–82 years, from 12 medical centers in Belgium, with an acute exacerbation of well-established, endoscopically and histologically proven left-sided UC, were included. The colonic extension was endoscopically determined at the time of the initial diagnosis and at the actual flare-up. The mean duration of UC was 93+72 months, median was 84 months, and range was 3–372 months. Active smoking was reported in only 7% of patients, while the majority were no-smokers (63%) or ex-smokers (30%). The median colonic extension at the time of initial diagnosis was 25 cm, range 2–70 cm from the anal merge. Sixty-six percent of the patients had quiescent disease without flare-ups during last year. The χ2-test was used for statistical analysis. Results29/98 (29.6%) patients had not used any maintenance therapy in the last 3 months before the actual exacerbation. The most commonly used maintenance therapy was 5-ASA (43%), while combined therapy with 5-ASA, corticosteroids or immunosuppresives (mainly azathioprine) in all possible combinations was reported by 29.6% of patients. The extent of UC had not changed in 50.7% and 51.7% of patients, respectively, with and without maintaining therapy (NS, p=0.99). Some degree of regression was observed in, respectively, 21.7% and 20.7% (NS, p=0.99), and some degree of extension in, respectively, 27.5% and 27.6% (NS, p=0.99). Furthermore, no relationship was found between changes in colonic extent and type of maintaining therapy, smoking habits or disease activity during the last year before the acute exacerbation. A tendency of beneficial effect of maintenance therapy on disease extent was observed in patients with continuous active disease of short duration. ConclusionsAccording to this multicenter study, maintenance remission therapy for left-sided UC was not found to have a statistically significant effect on colonic extension. Further long-term studies are necessary to confirm these results.

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

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. 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. 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). 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.

Curcumin Maintenance Therapy for Ulcerative Colitis: Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial

Curcumin is a biologically active phytochemical substance present in turmeric and has pharmacologic actions that might benefit patients with ulcerative colitis (UC). The aim in this trial was to assess the efficacy of curcumin as maintenance therapy in patients with quiescent ulcerative colitis (UC). Eighty-nine patients with quiescent UC were recruited for this randomized, double-blind, multicenter trial of curcumin in the prevention of relapse. Forty-five patients received curcumin, 1g after breakfast and 1g after the evening meal, plus sulfasalazine (SZ) or mesalamine, and 44 patients received placebo plus SZ or mesalamine for 6 months. Clinical activity index (CAI) and endoscopic index (EI) were determined at entry, every 2 months (CAI), at the conclusion of 6-month trial, and at the end of 6-month follow-up. Seven patients were protocol violators. Of 43 patients who received curcumin, 2 relapsed during 6 months of therapy (4.65%), whereas 8 of 39 patients (20.51%) in the placebo group relapsed (P=.040). Recurrence rates evaluated on the basis of intention to treat showed significant difference between curcumin and placebo (P=.049). Furthermore, curcumin improved both CAI (P=.038) and EI (P=.0001), thus suppressing the morbidity associated with UC. A 6-month follow-up was done during which patients in both groups were on SZ or mesalamine. Eight additional patients in the curcumin group and 6 patients in the placebo group relapsed. Curcumin seems to be a promising and safe medication for maintaining remission in patients with quiescent UC. Further studies on curcumin should strengthen our findings.

Infliximab for induction and maintenance therapy for ulcerative colitis

Infliximab for induction and maintenance therapy for ulcerative colitis

Review article: high‐dose aminosalicylates to induce and maintain remissions in ulcerative colitis

Sulfasalazine was the first aminosalicylate to be used for induction and maintenance therapy of ulcerative colitis (UC). Initial trials demonstrated a dose response that was compromised by dose-related intolerance. Recognition that the 5-aminosalicylic acid moiety (5-ASA, mesalazine) is the active ingredient of sulfasalazine has allowed the development of sulpha-free formulations of mesalazine and alternative azo-bond derivatives (olsalazine, balsalazide) that substantially reduce the dose-related (and allergic) consequences of the sulfapyridine moiety of sulfasalazine. Dose-ranging studies of mesalazine formulations for induction of remission have demonstrated increased efficacy of oral mesalazine up to 4-4.8 g/day, particularly in patients with more moderate disease activity. Combination therapy with oral and rectal mesalazine provide additional efficacy for patients with both distal and extensive colitis. The mesalazine formulations have dose-related benefits without dose-related side effects. In contrast, the azo-bond formulations are compromised by secretory diarrhoea at doses providing greater than 2-2.4 g/day of mesalazine. There are less data regarding dose-related benefits of aminosalicylates to maintain remissions in UC greater than 1.6 g/day of mesalazine, although the absence of dose-related side effects allows continuation of the same inductive dose through maintenance treatment without dose-related toxicity.

Probiotics

There is currently a growing appreciation for the role of the enteric flora in health and disease. In the past years overwhelming evidence has accumulated for the role of commensal gut bacteria in the inflammatory bowel diseases Crohn's disease and ulcerative colitis. Both entities are mainly located in areas with high bacterial concentrations. Reduction of the enteric bacterial concentration by antibiotics, lavage, or surgical bypass results in a mitigation of symptoms, while experimental colitis models depend on the presence of the bacterial flora and the NOD2/CARD15-mutation results in inefficient clearance of invasive bacteria. Those findings helped to bring the concept of probiotic therapy to the forefront, a therapy that had been known for millennia, but had been disregarded by the scientific world. Probiotics are meanwhile established in the maintenance therapy of ulcerative colitis and chronic recurrent or refractory pouchitis. Promising data exist for the primary prevention of pouchitis. Probiotic research at the intersection of gastroenterology, immunology and microbiology is highly dynamic in both the basic and the clinical field. Further understanding of the complex molecular mechanisms leading to the effectiveness of probiotics will also spur the development of more successful probiotic formulations.

Incidence of Colectomy During Long-term Follow-up After Cyclosporine-Induced Remission of Severe Ulcerative Colitis

Cyclosporine (CSA) has been shown to be effective in steroid-refractory ulcerative colitis (UC) and as an alternative to glucocorticosteroids in patients with severe attacks of UC. Our aim was to investigate the long-term efficacy of CSA. We conducted a retrospective cohort study of all patients admitted to our institution with an attack of UC treated with intravenous CSA between November 1992 and October 2004. Patients who responded to intravenous CSA were switched to Neoral for 3 months. Kaplan-Meier curves were used for survival analysis with quantitative variables compared using a 2-tailed Student t test with qualitative variables and differences compared with a chi(2) analysis. A total of 118 (83%) of the 142 patients had an initial response to CSA and avoided colectomy during hospitalization. Of the 118 patients, 41 (35%) [corrected] required a future colectomy. The rate of colectomy in those already on azathioprine compared with those starting azathioprine concurrently with CSA was 59% vs 31%, respectively (P < .05). Also, 88% of patients already on azathioprine and requiring colectomy underwent surgery within the first year of receiving CSA. Life-table analysis shows that although only 33% of patients require colectomy at 1 year, 88% will require colectomy at 7 years. CSA is an effective short- to medium-term treatment for patients with severe UC but at 7 years, 88% of patients will require a colectomy. Azathioprine-naive patients have better outcomes.

Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis

BACKGROUND: Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor α, is an established treatment for Crohn‘s disease but not ulcerative colitis. METHODS: Two randomized, double-blind, placebo-controlled studies -the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively) -evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2. RESULTS: In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P 0.001 for both comparisons with placebo). A response was defined as a decrease in the Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute rectal-bleeding subscore of 0 or 1. In ACT 2, 64 percent of patients who received 5 mg of infliximab and 69 percent of those who received 10 mg had a clinical response at week 8, as compared with 29 percent of those who received placebo (P 0.001 for both comparisons with placebo). In both studies, patients who received infliximab were more likely to have a clinical response at week 30 (P ≤0.002 for all comparisons). In ACT 1, more patients who received 5 mg or 10 mg of inflix imab had a clinical response at week 54 (45 percent and 44 percent, respectively) than did those who received placebo (20 percent, P0.001 for both comparisons) . CONCLUSIONS: Patients with moderate-to-severe active ulcerative colitis treated with infliximab at weeks 0, 2, and 6 and every eight weeks thereafter were more likely to have a clinical response at weeks 8, 30, and 54 than were those receiving placebo.

Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis

Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis

Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis

Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor alpha, is an established treatment for Crohn's disease but not ulcerative colitis. Two randomized, double-blind, placebo-controlled studies--the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively)--evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2. In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P<0.001 for both comparisons with placebo). A response was defined as a decrease in the Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute rectal-bleeding subscore of 0 or 1. In ACT 2, 64 percent of patients who received 5 mg of infliximab and 69 percent of those who received 10 mg had a clinical response at week 8, as compared with 29 percent of those who received placebo (P<0.001 for both comparisons with placebo). In both studies, patients who received infliximab were more likely to have a clinical response at week 30 (P< or =0.002 for all comparisons). In ACT 1, more patients who received 5 mg or 10 mg of infliximab had a clinical response at week 54 (45 percent and 44 percent, respectively) than did those who received placebo (20 percent, P<0.001 for both comparisons). Patients with moderate-to-severe active ulcerative colitis treated with infliximab at weeks 0, 2, and 6 and every eight weeks thereafter were more likely to have a clinical response at weeks 8, 30, and 54 than were those receiving placebo. (ClinicalTrials.gov numbers, NCT00036439 and NCT00096655.)

Infliximab induction and maintenance therapy for ulcerative colitis: the ACT 2 trial

Background: The efficacy of infliximab (IFX) for the treatment of ulcerative colitis (UC) was previously unknown. Two Phase 3 trials, ACT I and ACT 2, evaluated the safety and efficacy of IFX for treatment of active UC. Results from ACT 2 are presented.

Comparison of two different daily dosages (2.4 vs. 1.2 g) of oral mesalazine in maintenance of remission in ulcerative colitis patients: 1‐year follow‐up study

Mesalazine as maintenance therapy in ulcerative colitis is used worldwide and has been proven to be effective. However, the optimal dosage remains to be defined. To establish whether daily treatment with 2.4 g of oral mesalazine is more effective than 1.2 g in preventing disease relapse. A total of 156 patients with ulcerative colitis in remission were randomly treated for 1 year with 2.4 (n = 80) or 1.2 (n = 76) g/day of mesalazine. Activity of disease was assessed by periodical clinical, endoscopic and histological examinations. After 12 months, 24 of 80 patients (30%) on 2.4 g and 20 of 76 patients (26%) on 1.2 g were still in remission (P = N.S.). Patients in 2.4 g group remained in remission for a longer time than those in 1.2 g group (P < 0.001). Among clinical variables considered in the study, course of disease prior to enrollment (< or = 3 or > 3 relapses/year) was found to influence response to therapy. A daily dosage of 2.4 g of oral mesalazine seems to better at preventing and delaying relapses of ulcerative colitis than 1.2 g. The course of disease seems to be crucial in choosing the optimal dosage of mesalazine in a maintenance regimen.

Review article: antibiotics and probiotics in inflammatory bowel disease.

Treatment with antibiotics in inflammatory bowel disease has a long tradition and is widely used. The indications for antibiotic therapy are wide ranging, from specific situations such as abscesses or fistulae, to patients with severe disease (as an unspecific 'protective' measure), and to address the hypothesis that the enteric flora as a whole, or specific microorganisms such as mycobacteria, are involved in the pathogenesis of inflammatory bowel disease. The best-studied single antibiotic compound is metronidazole. However, overall, the scientific basis for the use of antibiotics is limited, which may reflect a lack of interest from sponsors within the pharmaceutical industry. Despite this weak evidence base, antibiotics are a globally established therapeutic tool in inflammatory bowel disease. Growing evidence from human and animal studies points towards a pivotal pathogenetic role of intestinal bacteria in inflammatory bowel disease. In view of these experimental findings, clinical trials have been undertaken to elucidate the therapeutic effects of probiotics in inflammatory bowel disease. Probiotics are viable nonpathogenic microorganisms which confer health benefits to the host by improving the microbial balance of the indigenous microflora. So far, of the many candidates, one specific strain (Escherichia coli Nissle 1917) and a mixture of eight different bacteria have demonstrated convincing therapeutic efficacy in controlled studies. Maintenance therapy in ulcerative colitis and prevention therapy, as well as the treatment of pouchitis, have emerged as areas in which probiotic therapy offers a valid therapeutic alternative to current treatments. Further investigations may detect additional clinically effective probiotics and other clinical indications.

Guidelines for the treatment of ulcerative colitis in remission.

The role is reviewed of sulphasalazine, 5-aminosalicylic acid (5-ASA), immunosuppressive agents and corticosteroids in the maintenance treatment of ulcerative colitis in remission. Sulphasalazine and oral 5-ASA are the drugs of first choice in preventing relapses for patients suffering from intermittent chronic ulcerative colitis. Rectally administered 5-ASA may be a valid alternative for treating patients with proctitis and left-sided ulcerative colitis. The optimal dosage of oral 5-ASA in the maintenance therapy of ulcerative colitis in remission is not clear. However, there is evidence that a higher dose of 5-ASA is more effective than low dosage in preventing relapses in patients in remission. For patients with chronically active or steroid-dependent ulcerative colitis who have achieved remission while taking immunosuppressants, continuing azathioprine or 6-mercaptopurine is indicated. Existing data cast doubts as to whether or not continuous maintenance is still necessary in patients suffering from intermittent chronic ulcerative colitis with prolonged endoscopic, clinical and histological remission.

Oral mesalamine was effective and safe in maintaining remission in ulcerative colitis

Source Citation The Mesalamine Study Group. An oral preparation of mesalamine as long-term maintenance therapy for ulcerative colitis. A randomized, placebo-controlled trial. Ann Intern Med. 1996 J...

Transdermal Nicotine as Maintenance Therapy for Ulcerative Colitis

Ulcerative colitis is largely a disease of nonsmokers. Having found previously that treatment with transdermal nicotine patches and mesalamine (5-aminosalicylic acid) has a beneficial effect on active colitis, we examined the value of transdermal nicotine for the maintenance of remission. We treated 80 patients with ulcerative colitis in remission with either transdermal nicotine or placebo patches for six months in a randomized, double-blind study. Incremental doses of nicotine were given for the first three weeks to achieve a maintenance dose; most patients tolerated 15 mg for 16 hours daily. All patients were taking mesalamine preparations as maintenance treatment at entry into the study; this treatment was stopped once the maintenance dose of nicotine was achieved. Clinical, sigmoidoscopic, and histologic assessments were made at the beginning and the end of the study, or at relapse. Side effects and serum nicotine and cotinine concentrations were monitored throughout the study. There was no significant difference in the number of relapses between the groups. Twenty-two patients in the nicotine group were prematurely withdrawn from the study, 14 because of relapse and 8 for other reasons, including side effects and protocol violations. In the placebo group, 20 patients were withdrawn prematurely, 17 because of relapse and 3 for other reasons. Among patients using 15-mg nicotine patches, serum nicotine and cotinine concentrations were lower than expected and may reflect poor compliance. Side effects were reported by 35 patients--21 in the nicotine group and 14 in the placebo group--the most common of which were nausea, lightheadedness, and itching. Transdermal nicotine alone was no better than placebo in the maintenance of remission of ulcerative colitis, and premature withdrawal due to side effects was more common in the nicotine group.

Double-blind comparison between mesalamine (salofalk) and a preparation of viable E. coli nissle 1917 (mutaflor) for maintenance therapy of ulcerative colitis: [formula omitted]. University of Cologne, E. Schütz, Fachpraxis, Regensburg, M. Stolte, Pathologisches Institut, Bayreuth, Germany, B. Fixa, Hradec Kralove, P. Fric, Praha, Charles University, Czech Republic, G. Judmaier, University Innsbruck, Austria

Double-blind comparison between mesalamine (salofalk) and a preparation of viable E. coli nissle 1917 (mutaflor) for maintenance therapy of ulcerative colitis: [formula omitted]. University of Cologne, E. Schütz, Fachpraxis, Regensburg, M. Stolte, Pathologisches Institut, Bayreuth, Germany, B. Fixa, Hradec Kralove, P. Fric, Praha, Charles University, Czech Republic, G. Judmaier, University Innsbruck, Austria

Maintenance Therapy in Ulcerative Colitis and Crohnʼs Disease

Aminosalicylates are of proven benefit in maintaining medically induced remissions of both ulcerative colitis and Crohn's disease. Even rectal 5-aminosalicylic acid has been found to be useful in maintaining long-term remissions of distal ulcerative colitis. Particularly noteworthy is the demonstrated efficacy of oral mesalamine in reducing recurrence rates of Crohn's disease following ileocecal resection, if introduced within the first few weeks after surgery. In all cases, the efficacy of the aminosalicylates is dose related, with little benefit demonstrable, at least in Crohn's disease, at oral doses < 2 g/day. In contrast to aminosalicylates, corticosteroids and cyclosporine are better suited to the induction of rapid remissions of acute disease than to the maintenance of long-term remissions. Antimetabolites, especially azathioprine and 6-mercaptopurine, are highly beneficial and relatively safe for long-term steroid-sparing therapy in both ulcerative colitis and Crohn's disease, at least for those patients whose initial remissions have already been induced by these agents.