Prolonged-release mesalazine: a review of its therapeutic potential in ulcerative colitis and Crohn's disease

Prolonged-release mesalazine (Pentasa) consists of ethylcellulose-coated microgranules from which mesalazine (known in the US as mesalamine) is released in the small and large intestine in a diffusion-dependent manner. Dose-dependent improvements in clinical and endoscopic parameters have been reported with prolonged-release mesalazine 2 and 4 g/day in clinical trials in patients with mild to moderately active ulcerative colitis. Induction of clinical and endoscopic remission was achieved in more patients receiving a daily dosage of 4 g/day than in those receiving placebo. In patients with ulcerative colitis in remission, prolonged-release mesalazine is effective in reducing the rate of relapse. Higher dosages tend to be more effective, and a 12-month remission rate of 64% has been reported for patients treated with a 4 g daily dosage of this formulation. Comparative data indicate that prolonged-release mesalazine has similar efficacy in maintaining remission to molar equivalent doses of sulfasalazine. Data from a study in patients with mild to moderately active Crohn's disease indicates that higher dosages (4 g/day) of prolonged-release mesalazine are more effective than placebo in reducing disease activity. After 16 weeks' treatment, 64% of patients receiving a 4 g/day dosage experienced clinical improvement and 43% attained remission. In studies of patients in remission of Crohn's disease, the formulation appears to be more effective in preventing relapse in patients with isolated small bowel disease than in those with colonic involvement. The tolerability profile of oral prolonged-release mesalazine is similar to that of placebo and the incidence of adverse events does not appear to be dose-related. Nausea/vomiting, diarrhoea, abdominal pain and dyspepsia occur most frequently, although their incidence is low. Reports of nephrotoxicity during prolonged-release mesalazine treatment are rare. Conclusions: Oral prolonged-release mesalazine is effective for maintenance and induction of remission of mild to moderately active colitis, both in patients with distal disease and in those with pancolitis. The formulation has similar efficacy to that of equimolar concentrations of sulfasalazine. Prolonged-release mesalazine also appears to be effective in the treatment of Crohn's disease, and maintenance therapy is of particular value in patients with isolated small bowel involvement. Evidence suggests that higher dosages (3 to 4 g/day) of prolonged-release mesalazine have additional therapeutic benefits over lower dosages in patients with inflammatory bowel disease without increasing the incidence of adverse events.     

Oral delayed-release mesalazine: a review of its use in ulcerative colitis and Crohn's disease

Oral delayed-release mesalazine is an enteric-coated formulation which releases mesalazine in the terminal ileum and colon. Up to 74% of patients with mild to moderately active ulcerative colitis experience endoscopic or symptomatic improvement (including remission) or both when treated with oral delayed-release mesalazine 2.4 to 4.8 g/day. There is a trend towards a better response in patients receiving higher daily dosages of oral delayed-release mesalazine, especially in patients with active distal disease. In patients with left-sided ulcerative colitis, oral balsalazide 6.75 g/day appears to be more effective than oral delayed-release mesalazine 2.4 g/day, but a higher dosage of oral delayed-release mesalazine 4.8 g/day may provide additional benefit in these patients. Oral delayed-release mesalazine 0.8 to 4.4 g/day appears to be as effective as sulfasalazine 2 to 4 g/day, prolonged-release mesalazine 1.5 g/day or balsalazide 3 g/day in maintaining remission in patients with ulcerative colitis. The optimal dosage of oral delayed-release mesalazine for the maintenance of remission is unclear. However, oral delayed-release mesalazine 1.6 g/day with rectal mesalazine 4g, administered twice weekly, was more effective than oral drug alone in maintaining remission in patients at high risk of relapse. In patients with left-sided or distal disease oral olsalazine 1 g/day appeared to be superior to oral delayed-release mesalazine 1.2 g/day for maintenance of symptomatic remission. Limited data in patients with Crohn's disease have shown oral delayed-release mesalazine 0.4 to 4.8 g/day to be an effective therapy for active disease (remission in up to 45% of patients) and for quiescent disease (relapse in 34% of recipients over a duration of up to 12 months). Preliminary data indicate that oral delayed-release mesalazine 2.4 g/day is effective in preventing postoperative recurrence of Crohn's disease. Oral delayed-release mesalazine is effective and well tolerated in sulfasalazine-intolerant patients with ulcerative colitis or Crohn's disease. CONCLUSIONS: Oral delayed-release mesalazine is effective in patients with mild to moderately active or quiescent ulcerative colitis. Available data suggest that patients with left-sided or distal ulcerative colitis are likely to require higher daily dosages of oral delayed-release mesalazine or supplementation with rectal mesalazine. Oral delayed-release mesalazine also appears to be effective in active and quiescent Crohn's disease. The drug is well tolerated and it appears to be effective in sulfasalazine-intolerant patients.     

Drug Therapy of Inflammatory Bowel Disease

Although the etiology of inflammatory bowel disease is unknown and specific therapy is unavailable, enough information on existing empiric agents is availble to allow rational therapy. These agents include sulfasalazine, steroids, immunosuppressive drugs, metronidazole and cholestyramine. Sulfasalazine is a two-part molecule that depends on bacterial cleavage in the colon to deliver locally acting 5-aminosalicylate, whose mechanism of action may relate to inhibition of prostaglandin synthesis. The other half of the molecule, sulfapyridine, is responsible for most of the side effects of the drug. While the efficacy of sulfasalazine in the treatment and prevention of attacks of ulcerative colitis is well established, its use in Crohn's disease appears to be limited to patients with active colitis and ileo-colitis. Sulfasalazine is of major benefit in preventing relapses in patients with ulcerative colitis in remission. New formulations of 5-aminosalicylate may allow delivery of the apparently active moiety to the small bowel and colon without concomitant sulfapyridine toxicity. Corticosteroids are highly effective in acute attacks of ulcerative colitis and Crohn's ileitis and ileo-colitis; the mechanism of antiinflammatory action remains speculative. However, maintenance therapy with steroids is ineffective in preventing relapses or recurrent attacks of either ulcerative colitis or Crohn's disease. Steroid enemas allow topical administration to patients with distal colitis and proctitis with few systemic side effects. In children with growth failure associated with active Crohn's disease, amelioration by steroid therapy may actually restore normal growth. Immunosuppressive agents such as azathioprine and 6-mercaptopurine are of little value in active Crohn's disease when administered alone; however, in combination with other agents they may help diminish steroid dose, close fistulae and prevent relapse. Their mode of action likely depends on long-term cytostatic effects on immune effector cells. Concern for leukopenia and the development of late malignancy has limited their use to patients not responding to other therapies. Metronidazole, an antimicrobial agent that is effective against anaerobes, has recently been shown useful in Crohn's disease involving the colon and perianal area. Its mechanism of action is uncertain, but may be related to its antibacterial actions on anaerobes. Cholestyramine can be successfully used to control bile salt-induced diarrhea in Crohn's patients with terminal ileal resections. Effective drug therapy of inflammatory bowel disease is only part of a total program of management including reassurance, frequent explanations, well-timed use of surgery, and an understanding physician.     

Promising new agents for the treatment of inflammatory bowel disorders

A groundswell of therapeutic modalities is presently sweeping through the field of inflammatory bowel disease (IBD), revolutionising the treatment and management of these disorders. At the forefront of newer agents are biological therapies, also referred to as 'biologics'. These include infliximab (cA2), CDP 571, rhIL-10, ICAM-1 antisense oligonucleotide (ISIS 2302) and opreleukin (rhIL-11). Among these, infliximab and CDP 571 are perhaps the most promising, particularly in Crohn's disease. Both are anti-TNF alpha monoclonal antibody formulations with proven efficacy at doses of 5 mg/kg for inducing remission in patients with moderate to severe refractory Crohn's disease. Infliximab is beneficial in the treatment of fistulous Crohn's disease as well. Anti-inflammatory cytokines such as rhIL-10 and opreleukin (rhIL-11) in early reports appear efficacious in Crohn's disease but not in ulcerative colitis. Budesonide, a second generation glucocorticoid, in an oral controlled ileal release capsule, is an attractive alternative to prednisone for treating active Crohn's disease of the distal ileum and proximal colon. Also available as an enema, budesonide's efficacy approximates that of prednisolone for inducing remission in active distal ulcerative colitis. Postoperative recurrences of Crohn's disease are a common clinical scenario. Recently, mesalazine, metronidazole and mercaptopurine have been re-evaluated in the postoperative setting. In the largest postoperative prophylaxis trial, mercaptopurine was superior to both placebo and mesalazine in preventing clinical, endoscopic and radiographic relapses. Finally, miscellaneous therapies such as transdermal nicotine, nicotine tartrate enemas and topical lidocaine used in pilot studies for ulcerative colitis have shown promise. Case reports of thalidomide and tacrolimus (FK 506) have reported beneficial effects in treating complicated, refractory Crohn's disease.     

The use of tacrolimus in the treatment of inflammatory bowel disease

Tacrolimus is a calcineurin inhibitor that suppresses pro-inflammatory cytokine production and T-cell activation. These immunosuppressant effects have been used to treat inflammatory bowel disease, especially fistulising Crohn's disease and refractory ulcerative colitis. The more predictable oral bioavailability and better side-effect profile makes tacrolimus a more favourable choice as compared with ciclosporin. Dose-dependent side effects, such as nephrotoxicity, are reported but are mostly reversible with dose reduction or cessation of therapy. Topical tacrolimus has also been used to treat pyoderma gangrenosum, an extra-intestinal manifestation of inflammatory bowel disease. Tacrolimus is well-tolerated and should be considered as an alternative agent in the treatment of inflammatory bowel disease, especially those intolerant or refractory to the more conventional immunomodulators.     

Review article: new developments in the use of 5-aminosalicylic acid in patients with inflammatory bowel disease

Sulphasalazine is composed of sulphapyridine and mesalazine (5-aminosalicylic acid, 5-ASA or mesalazine) joined by an azo bond. Sulphasalazine has been used clinically for 40 years but less than 10 years ago it was recognized that the active moiety is 5-ASA. Sulphapyridine appears to act only as a carrier molecule to deliver mesalazine to the bowel, yet it is the sulphapyridine which appears to be responsible for many of the adverse effects observed with sulphasalazine. Normally, mesalazine is rapidly absorbed from the upper gastrointestinal tract. Since the action of mesalazine is thought to be locally at the site of disease in the intestine, the 5-ASA must be 'protected' to ensure its release in the terminal ileum and colon, the site of bowel inflammation in patients with Crohn's disease or ulcerative colitis. Recent clinical studies have confirmed the efficacy of topical (suppositories and enemas) therapy for ulcerative proctitis and left-sided colitis; oral mesalazine has been proven to be useful for the treatment of acute ulcerative colitis and for the maintenance of remission. There is preliminary evidence for the clinical usefulness of mesalazine in acute Crohn's disease as well as for the maintenance of remission.     

Medical management of Crohn's disease

Crohn's disease is a chronic inflammatory bowel disease of unknown etiology. Sulfasalazine and the newer 5-aminosalicylates remain the first agents of choice to treat mild to moderate disease and often are effective at high doses as maintenance therapies. Corticosteroids are often required to treat more moderate to severe disease activity, although approximately one-third of patients become steroid-dependent after a steroid-induced remission. Corticosteroids have proven ineffective in maintaining remission and side effects resulting from prolonged exposure preclude their long-term use. Azathioprine and 6-mercaptopurine are effective in the setting of steroid dependence and steroid resistance, as well as for the treatment of perianal and fistulizing complications unresponsive to antibiotics. Crohn's disease commonly recurs following surgical resection, and there is expanding evidence that postoperative prophylaxis with certain antibiotics (e.g., metronidazole), aminosalicylates or immunomodulators may be beneficial in the prevention of disease recurrence following resection. Cyclosporin may benefit patients with severe Crohn's disease or refractory fistulas. Recent trials of newer immunosuppressive agents commonly employed in transplant recipients and ongoing development of a new class of "biologic" agents targeting specific sites in the immunoinflammatory cascade, are expanding the pharmacological armamentarium available to treat certain patients.     

Mesalazine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in chronic inflammatory bowel disease

Mesalazine (5-aminosalicylic acid; mesalamine), the active moiety of sulphasalazine (salazosulfapyridine), is available in specially formulated oral and rectal forms for the treatment of active ulcerative colitis of mild to moderate severity and for maintenance therapy during disease remission. Tablets or capsules coated with acrylic-based resin and tablets containing microgranules coated with ethylcellulose deliver mesalazine to the distal small intestine and colon, thus avoiding the need for the carrier, sulphapyridine, which is responsible for many of the adverse effects associated with sulphasalazine. Since mesalazine is released in the small intestine from some coated preparations in contrast to sulphasalazine, these oral formulations have therapeutic potential in Crohn's disease. A limited number of therapeutic trials suggest that orally administered mesalazine 1.5 to 2.4g daily is of similar efficacy to sulphasalazine 2 to 3g daily in patients with mild to moderate ulcerative colitis. The efficacy of mesalazine enemas has been more widely investigated, a dose of 1 to 4g once daily being consistently more effective than placebo and apparently similar to enemas of prednisone 25mg or oral sulphasalazine 3g. Initial results suggest that mesalazine 4g enemas may be more effective than those containing hydrocortisone 100mg. Mesalazine and sulphasalazine in approximately equivalent oral dosages are similarly effective in maintaining remission in ulcerative colitis. Orally administered coated mesalazine is generally well tolerated by about 85% of patients allergic to or intolerant of sulphasalazine, the remainder experiencing similar reactions to both drugs. Adverse effects of mesalazine enemas are confined to local irritation and effects resulting from enema-tip insertion. Thus, orally administered coated mesalazine is a suitable alternative to sulphasalazine in the treatment of patients with mild to moderate active distal ulcerative colitis and for maintaining remission particularly in patients allergic to or intolerant of sulphasalazine. In patients who find enema therapy acceptable, mesalazine enemas are effective and well tolerated.     

Immunosuppressive drugs in inflammatory bowel disease. A review of their mechanisms of efficacy and place in therapy

Immune effector mechanisms are central to the disease process in inflammatory bowel disease, but it is not clear whether the mucosal or systemic immunological abnormalities are primary phenomena, or are secondary to disease activity. Corticosteroid drugs remain the most effective treatment for active disease, but there is no evidence that they are useful for maintenance therapy. Some patients, however, are dependent on low-dose corticosteroids, and relapse when the drug is withdrawn. These drugs have widespread actions on the immune response, and monocytes are particularly sensitive to corticosteroids. In contrast, sulphasalazine and 5-aminosalicylic acid are effective in maintenance therapy, but do not act primarily by immunosuppressive mechanisms. They are effective in maintenance therapy of ulcerative colitis, and mild relapses of ulcerative colitis and colonic Crohn's disease. New preparations of 5-aminosalicylic acid have reduced side effects, many of which are due to sulphapyridine. Azathioprine and 6-mercaptopurine are used less widely: in Crohn's disease there is reasonable evidence for benefit in chronic active disease unresponsive to corticosteroids, and maintenance of remission. In ulcerative colitis, the position is less clearcut. Overall, trials favour an effect in chronic active disease, and there are pointers to an effect in maintenance of remission. Because of their side effects, in particular marrow suppression, these drugs should be reserved for second-line therapy. Similarly, other cytotoxic drugs are not used because of their side effects. More recently, cyclosporin A, with its selective action on interleukin-2 release and/or synthesis, and inhibition of helper T cell function, has been shown to be helpful in Crohn's disease. At present it should only be used in controlled trials, for patients with unresponsive disease in whom surgery is contraindicated. Renal toxicity may limit long term use. There is little data for cyclosporin A in ulcerative colitis. On the basis that there may be an underlying immune defect in Crohn's disease leading to mucosal inflammation, immunostimulant therapy has been used, but there is no evidence for benefit from treatment with BCG or levamisole in active disease or in maintenance therapy. 7S-Immunoglobulin, plasmapheresis or T-lymphocyte apheresis have been used in acute relapse, but evidence is anecdotal, and does not support their use except as a desperate measure to avoid surgery. Further well-designed controlled trials are needed to define the role of all these drugs, and further research into the mechanism of action on the immune response may shed light on the pathogenesis of inflammatory bowel disease.     

Efficacy and tolerability of oral iron therapy in inflammatory bowel disease: a prospective, comparative trial

BACKGROUND: In patients with inflammatory bowel disease, oral iron is anecdotally reported to be less effective and less well tolerated than in those without inflammatory bowel disease, and to increase disease activity. AIM: To study prospectively the effects of oral iron in patients with and without inflammatory bowel disease. METHODS: Patients with ulcerative colitis, Crohn's disease and non-inflammatory bowel disease controls, all with iron deficiency anaemia, were assessed with symptom diaries, a quality of life questionnaire (Inflammatory Bowel Disease Questionnaire; inflammatory bowel disease patients only) and blood tests to measure iron repletion, disease activity and antioxidant capacity before and after starting 4 weeks of oral iron. In patients with ulcerative colitis, sigmoidoscopic scoring and rectal biopsies for reactive oxygen metabolite production were performed before and after iron therapy. RESULTS: All groups showed increases in haemoglobin and ferritin. Iron intolerance occurred in about a quarter of patients in each group. Two of 33 (6%) of inflammatory bowel disease patients had a relapse during treatment. Symptoms worsened in ulcerative colitis, but not in Crohn's disease or non-inflammatory bowel disease patients; Inflammatory Bowel Disease Questionnaire scores improved in ulcerative colitis. Laboratory markers of disease activity, sigmoidoscopic scores, histological scores, antioxidant capacity levels and reactive oxygen metabolite production did not change. CONCLUSIONS: Oral iron is equally efficacious and well tolerated in inflammatory bowel disease and non-inflammatory bowel disease patients. A tiny minority of inflammatory bowel disease patients relapse in association with use of oral iron therapy.     

益生菌制剂在轻中度溃疡性结肠炎治疗中的作用

目的 观察益生菌制剂对轻、中度溃疡性结肠炎的临床疗效.方法 第一阶段将129例轻、中度溃疡性结肠炎患者随机分成治疗组(65例)和对照组(64例),分别予以益生菌和美拉沙嗪治疗,治疗12周后观察两组缓解率及缓解时间.第二阶段将缓解后91例患者随机分成治疗组(43例)和对照组(48例),分别予以益生菌和美拉沙嗪治疗,治疗12周后观察两组维持时间及复发率.结果 第一阶段两组患者治疗后缓解率及达到临床缓解时间无明显统计学差异(P＞0.05);第二阶段两组患者治疗后维持缓解时间及复发率无明显统计学差异(P＞0.05).结论 益生菌能够有效治疗轻、中度活动性溃疡性结肠炎,并有效预防复发.     

Efficacy and safety of thalidomide in children and young adults with intractable inflammatory bowel disease: long-term results

BACKGROUND: Anti-tumour necrosis factor-alpha antibodies are useful for the treatment of refractory Crohn's disease and ulcerative colitis. Thalidomide is another agent with tumour necrosis factor-alpha suppressive properties. AIM: To investigate the long-term efficacy and safety of thalidomide in a group of children and young adults with refractory inflammatory bowel disease. METHODS: Twenty-eight patients with refractory moderate-severe inflammatory bowel disease (19 Crohn's disease, 9 ulcerative colitis) received thalidomide 1.5-2.5 mg/kg/day. Patients were assessed at baseline, at weeks 2, 4, 8 and 12, and then every 12 weeks by patient's diary, physical examinations, laboratory analyses and scoring on activity indexes. Primary outcomes were: (i) efficacy in inducing remission; and (ii) efficacy in maintaining remission. RESULTS: Remission was achieved with thalidomide in 21 of 28 (75%) patients (17 with Crohn's disease, 4 with ulcerative colitis). Mean duration of remission was 34.5 months. Sixteen of 20 (80%) patients suspended steroids. Reversible neuropathy occurred in seven of 28 (25%) patients, but only with cumulative doses over 28 g. Other side effects requiring thalidomide suspension were vertigo/somnolence (one of 28), and agitation/hallucinations (one of 28). CONCLUSIONS: Thalidomide seems to be effective in inducing long-term remission in children and adolescents with intractable inflammatory bowel disease. Neuropathy is the main adverse effect, but appears to be cumulative dose-dependent, thus allowing long-term remission before drug suspension.     

Olsalazine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in inflammatory bowel disease.

Olsalazine (sodium azodisalicylate; azodisal sodium) is an anti-inflammatory agent designed to deliver its active moiety, mesalazine (5-aminosalicylic acid; mesalamine), to the colon while avoiding the adverse effects associated with the use of a sulfapyridine carrier. As a prodrug, olsalazine is an effective oral treatment for both active ulcerative colitis and for maintenance of disease remission and may possibly be of benefit in patients with Crohn's colitis. Findings from both short and long term noncomparative and comparative studies demonstrate that olsalazine 1 to 3g daily in divided doses improves clinical signs and symptoms of colitis in approximately 60 to 80% of patients with acute ulcerative colitis of mild to moderate severity. This improvement rate was similar to that obtained with sulfasalazine. Lower doses of olsalazine, usually 1g daily in divided doses, also maintained remission in patients with chronic ulcerative colitis. While olsalazine effectively delivers mesalazine to the colon, the prodrug itself increases net luminal water secretion and accelerates gastrointestinal transit of a meal. The resulting diarrhoea (occurring in approximately 17% of patients and resulting in withdrawal from therapy in 6% of patients) is distinguishable from that associated with inflammatory bowel disease by the high water content and the absence of blood. Olsalazine-induced diarrhoea usually occurred soon after initiation of olsalazine therapy or dosage increase, was more frequent with higher doses and was usually transient. Dosage reduction, increases in frequency of dosing and concomitant administration with food reduced the severity in many patients with persistent olsalazine-induced diarrhoea. With the exception of diarrhoea, olsalazine was generally well tolerated. Fewer than 14% of patients allergic to or intolerant of sulfasalazine had similar reactions to olsalazine. Olsalazine appears to be a suitable therapy for the treatment of first attacks as well as acute exacerbation of mild to moderate acute ulcerative colitis, and for the maintenance of remission in patients with chronic ulcerative colitis.     

Patients with refractory Crohn's disease or ulcerative colitis respond to dehydroepiandrosterone: a pilot study

BACKGROUND: Dehydroepiandrosterone is a steroid hormone used as an 'over-the-counter' drug in the USA. Treatment with dehydroepiandrosterone was effective in randomized controlled trials in patients with systemic lupus erythematosus. Dehydroepiandrosterone sulphate concentrations are decreased in patients with inflammatory bowel disease. Dehydroepiandrosterone inhibits nuclear factor-kappaB and the secretion of interleukin-6 and interleukin-12 via the peroxisome proliferator-activated receptor alpha. AIM: A phase II pilot trial was started to evaluate the effect of dehydroepiandrosterone in active inflammatory bowel disease. METHODS: Twenty patients with chronic active inflammatory bowel disease [seven Crohn's disease (Crohn's disease activity index, 242 +/- 51; mean +/- s.d.); 13 ulcerative colitis (clinical activity index, 7.8 +/- 2.1)] took 200 mg dehydroepiandrosterone per day orally for 56 days. RESULTS: Six of the seven patients with Crohn's disease and eight of the 13 patients with ulcerative colitis responded to treatment, with a decrease in the Crohn's disease activity index of > 70 points and a decrease in the clinical activity index of > 4 points, respectively. Six Crohn's disease patients and six ulcerative colitis patients went into remission (Crohn's disease activity index < 150; clinical activity index 相似文献   

Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis

BACKGROUND: Aminosalicylates are the mainstay of therapy to prevent relapse of quiescent ulcerative colitis. The rationale for using probiotics is based on the evidence implicating intestinal bacteria in the pathogenesis of this disorder. AIM: To evaluate the efficacy of Lactobacillus GG alone or in combination with mesalazine vs. mesalazine as maintenance treatment in ulcerative colitis. PATIENTS AND METHODS: 187 ulcerative colitis patients with quiescent disease were randomized to receive Lactobacillus GG 18 x 10(9) viable bacteria/day (65 patients), mesalazine 2400 mg/day (60 patients) or Lactobacillus GG + mesalazine (62 patients). Disease activity index, endoscopic and histological scores were determined at 0, 6 and 12 months and in case of relapse. The primary end point was to evaluate sustained remission. RESULTS: Overall analysis showed no difference in relapse rate at 6 (P = 0.44) and 12 months (P = 0.77) among the three treatment groups. However, the treatment with Lactobacillus GG seems to be more effective than standard treatment with mesalazine in prolonging the relapse-free time (P < 0.05). CONCLUSIONS: Lactobacillus GG seems to be effective and safe for maintaining remission in patients with ulcerative colitis, and it could represent a good therapeutic option for preventing relapse in this group of patients.     

Systematic review: the use of mesalazine in inflammatory bowel disease

BACKGROUND: Mesalazine is among the medications most commonly prescribed by gastroenterologists, having to a large extent superseded sulfasalazine (sulphasalazine). However, there are still a number of aspects regarding its use which provoke debate and controversy. AIM: To provide a systematic assessment of the evidence for the use of mesalazine in ulcerative colitis and Crohn's disease. METHODS: References were identified using PubMed database. Additional references were identified with related article searches. RESULTS: Mesalazine has a clear role in the maintenance of remission in ulcerative colitis and management of mild to moderately active disease, although the efficacy of topical preparations or combined topical and oral is clearly superior to oral alone. Evidence that increasing the dose of oral mesalazine improves efficacy is not clear-cut. The benefits of mesalazine in the management of acute Crohn's disease and the maintenance of remission are questionable and alternative treatments are usually more appropriate. Emerging evidence suggests that maintenance mesalazine reduces the risk of neoplastic progression in chronic ulcerative colitis. Compliance with therapy is thus important, as is an understanding of individuals most likely to default on this. CONCLUSION: Evidence for a beneficial effect of mesalazine is largely confined to the management of ulcerative colitis.     

复方血竭与柳氮磺吡啶灌肠治疗溃疡性结肠炎的疗效观察

目的：比较复方血竭与柳氮磺吡啶（SASP）用灌肠方法治疗活动期溃疡性结肠炎的疗效和不良反应。方法：采用随机、双盲方法观察85例活动期溃疡性结肠炎的疗效和不良反应,疗程为20天。结果：治疗20天后复方血竭治疗组48例临床评价有效率为68.8%,内镜评价有效率为70.8%,组织学评价有效率为77.1%;SASP对照组37例临床评价有效率为45.9%,内镜评价有效率为48.6%,组织学评价有效率为54.1%。两组在临床、内镜及组织学评价上均有统计学差别（P〈0.05）。结论：用复方血竭和SASP灌肠方法治疗活动期溃疡性结肠炎均有良好疗效,无明显不良反应,且复方血竭优于SASP。     

Oral beclomethasone dipropionate: a critical review of its use in the management of ulcerative colitis and Crohn's disease

Crohn's disease and ulcerative colitis are inflammatory bowel diseases characterised by a chronic relapsing course. Corticosteroids represent the mainstay of medical treatment of inflammatory bowel disease for the induction of remission. Despite the high efficacy of systemic steroids, their use is limited by the high incidence of potentially serious adverse effects. The topically acting steroids are synthetic compounds characterised by high anti-inflammatory activity and low systemic effects by virtue of efficient first-pass hepatic inactivation. Budesonide and Beclomethasone Dipropionate are the two most studied topically acting steroids in inflammatory bowel disease. Oral Budesonide has been extensively studied in the treatment of mild to moderate ileo-caecal Crohn's disease but few data are available concerning oral Beclomethasone Dipropionate. This review focuses on the available evidence of efficacy and safety of oral Beclomethasone Dipropionate in the management of ulcerative colitis and Crohn's disease and a possible role of this steroid in clinical practice is suggested.     

Granulocyteaphaeresis in steroid-dependent inflammatory bowel disease: a prospective, open, pilot study

BACKGROUND: Uncontrolled studies suggest that granulocyteaphaeresis might be useful in the management of active ulcerative colitis. AIM: To assess the efficacy of granulocyteaphaeresis treatment in active steroid-dependent inflammatory bowel disease. METHODS: We conducted a multicentre, prospective, open, pilot study in patients with steroid-dependent inflammatory bowel disease. All patients were started on 60 mg/day of prednisone; after 1 week, a five-session programme of granulocyteaphaeresis (once per week) was started. The steroid dose was tapered weekly if there was clinical improvement. Remission was defined as an inactive clinical activity index together with complete withdrawal of steroids at week 6. The patients were followed up for at least 6 months or until disease relapse. RESULTS: Twenty-six patients (14 ulcerative colitis, 12 Crohn's disease) were included. More than a half had been previously treated with immunomodulators. Remission was achieved in 62 and 70% of ulcerative colitis and Crohn's disease, respectively. During a median follow-up of 12.6 months, six of eight ulcerative colitis patients maintained their clinical remission; however, only one Crohn's disease patient remained in remission after the first 6 months of follow-up. CONCLUSIONS: Granulocyteaphaeresis is a safe treatment option in inflammatory bowel disease. A five-session programme of granulocyteaphaeresis seems to be efficient in the treatment of steroid-dependent ulcerative colitis, but not in Crohn's disease.     

The efficacy of methotrexate for maintaining remission in inflammatory bowel disease

BACKGROUND: The management of patients with inflammatory bowel disease who are resistant to or intolerant of azathioprine remains a challenge. Low-dose methotrexate has been shown to be effective in inducing remission in Crohn's disease. AIM: This review was conducted because there are limited long-term follow-up data during and after stopping treatment. There are also limited data on the use of methotrexate in ulcerative colitis. METHODS: The study was a retrospective review of clinical notes. Remission was defined as minimal bowel symptoms without the need for oral steroids for 3 months. Relapse was defined as bowel symptoms that required steroid treatment or surgery. RESULTS: Seventy patients were reviewed; 48 had Crohn's disease and 22 had ulcerative colitis. The mean duration of treatment was 17.1 months; the mean maintenance dose was 20 mg weekly. Remission was achieved in 34 of 55 patients who completed more than 3 months of treatment (62%). Life-table analysis showed that the chances of remaining in remission at 12, 24 and 36 months (if treatment was continued) were 90%, 73% and 51%, respectively. The chances of remaining in remission after stopping treatment at 6, 12 and 18 months were 42%, 21% and 16%, respectively. The dose of methotrexate (mg/kg) was associated with the induction of remission (P=0.02). Treatment was equally effective for Crohn's disease and ulcerative colitis. CONCLUSIONS: Maintenance methotrexate treatment gives acceptable remission rates for treatment periods up to 3 years. After stopping treatment, relapse is frequent and occurs early (usually within 1 year).