Maintenance of remission in ulcerative colitis

Seventy percent of patients with ulcerative colitis can expect to experience a relapse over a 12 month period. Sulfasalazine was the first drug demonstrated to reduce this relapse rate to 21 percent. Subsequent studies have demonstrated that 5-aminosalicylic acid (5-ASA) is the main active component, and preparations containing only 5-ASA have similar efficacy to sulfasalazine. 5-ASA is readily absorbed from the small intestine; to achieve high a colonic lumenal concentration therefore requires special release formulation. A variety of 5-ASA preparations is available, differing in their release mechanism, efficacy and side effect profile. Most patients can be maintained in remission using oral 5-ASA medication. For patients with distal or left sided disease the use of rectal 5-ASA is also of proven benefit in maintaining remission. Some patients with frequent or severe relapses require stronger immunosuppression, and in these patients azathioprine or 6-mercaptopurine (6-MP) are of proven benefit. Azathioprine is also invaluable for maintaining remission in patients who have been treated with cyclosporin for a fulminant acute episode of colitis. The exciting spectre of natural bacterial therapies (probiotics) deserves further exploration.     

重视溃疡性结肠炎的维持缓解治疗

溃疡性结肠炎(UC)为终生不愈的疾病,现代治疗目标是尽快控制发作,取得更快的缓解,获得内镜下黏膜愈合,维持长期缓解,减少复发。新的治疗目标强调长期维持缓解治疗,达到完全黏膜愈合。坚持UC的维持缓解治疗>2年,可减少复发、降低发生结肠癌的风险、降低医疗费用。氨基水杨酸类制剂仍是轻、中度UC维持缓解的常用药物,免疫抑制药主要用于激素抵抗或依赖的难治性UC患者的维持缓解治疗,肾上腺皮质激素物一般不用于UC的维持缓解治疗。我国UC患者的易感基因可能与欧美国家的基因多态性位点不同,应依据我国UC的发病特征,制定有针对性的诊治意见。     

Short report: comparison of two doses of balsalazide in maintaining ulcerative colitis in remission over 12 months

In a four-centre prospective double-blind trial, 108 patients with ulcerative colitis in remission were randomized to receive balsalazide in doses of 3 g or 6 g/day for 12 months. The patients were assessed at 3-monthly intervals clinically, sigmoidoscopically and with routine haematology and biochemistry. Remission rates of 77% (3 g/day) and 68% (6 g/day) at 12 months were not significantly different. Intolerance reactions leading to withdrawal from the study occurred in only 9 patients (8%), all occurring in the first 7 weeks of the study. Balsalazide is therefore both highly effective in maintaining remission in ulcerative colitis and well tolerated in both conventional and high dosage (the latter equivalent to 5.5 g/day of sulphasalazine). In this study no distinct advantage in maintenance of remission has been found for the higher dose of balsalazide.     

Review article: defining remission in ulcerative colitis

Aliment Pharmacol Ther 2011; 34: 113–124

Summary

Background There is no international agreement on scoring systems used to measure disease activity in ulcerative colitis, nor is there a validated definition for disease remission. Aim To review the principles and components for defining remission in ulcerative colitis and propose a definition that will help improve patient outcomes. Methods A review of current standards of remission from the perspective of clinical trials, guidelines, clinical practice and patients was conducted by the authors. Selected literature focused on the components of a definition of remission, the utility of a definition and treatment strategies, based on current definitions. Results Different definitions of remission affect the assessment of outcome and make it difficult to compare trials. In the clinic, endoscopy is rarely used to confirm remission, because mucosal healing has only recently begun to be related to the duration of subsequent remission in a way that will affect clinical practice. Histopathology may be the ultimate arbiter of mucosal healing. There is no agreement on the definition of remission in current guidelines. Patient‐defined remission may predict endoscopic remission, but has yet to be shown to predict duration of remission. Conclusions A standard based on clinical symptoms and endoscopy is proposed. Histopathology is a third dimension of remission that may have prognostic value. The definition of remission should help predict long‐term outcome. The expectations of patients and their physicians need to be raised, as the goal of treatment of active ulcerative colitis should be to induce remission.     

Review article: maintenance of remission in ulcerative colitis

Seventy percent of patients with ulcerative colitis can expect to experience a relapse over a 12 month period. Sulfasalazine was the first drug demonstrated to reduce this relapse rate to 21 percent. Subsequent studies have demonstrated that 5-aminosalicylic acid (5-ASA) is the main active component, and preparations containing only 5-ASA have similar efficacy to sulfasalazine. 5-ASA is readily absorbed from the small intestine; to achieve high a colonic lumenal concentration therefore requires special release formulation. A variety of 5-ASA preparations is available, differing in their release mechanism, efficacy and side effect profile. Most patients can be maintained in remission using oral 5-ASA medication. For patients with distal or left sided disease the use of rectal 5-ASA is also of proven benefit in maintaining remission. Some patients with frequent or severe relapses require stronger immunosuppression, and in these patients azathioprine or 6-mercaptopurine (6-MP) are of proven benefit. Azathioprine is also invaluable for maintaining remission in patients who have been treated with cyclosporin for a fulminant acute episode of colitis. The exciting spectre of natural bacterial therapies (probiotics) deserves further exploration.     

Randomised clinical trial: a comparative dose-finding study of three arms of dual release mesalazine for maintaining remission in ulcerative colitis

Aliment Pharmacol Ther 2011; 33: 313–322

Summary

Background Comparative data regarding different regimens of oral mesalazine (mesalamine) for maintaining remission in ulcerative colitis are limited. Aim To evaluate whether 3.0 g mesalazine once‐daily (OD) is superior to the standard treatment of 0.5 g mesalazine three times daily (t.d.s.) and to prove the therapeutic equivalence of OD vs. t.d.s. dosing of total 1.5 g mesalazine for remission maintenance in patients with ulcerative colitis. Methods A 1‐year, multicentre, double‐blind, double‐dummy study was undertaken in patients with endoscopically and histologically confirmed ulcerative colitis in remission. Patients were randomised to oral mesalazine 3.0 g OD, 1.5 g OD or 0.5 g t.d.s. The primary efficacy endpoint was the proportion of patients still in clinical remission at the final visit, with clinical relapse being defined as CAI score >4 and an increase of ≥3 from baseline. Results The primary efficacy endpoint occurred in 162/217 3.0 g OD patients (75%), 129/212 1.5 g OD patients (61%) and 150/218 0.5 g t.d.s. patients (69%) in the intention‐to‐treat population, and in 152/177 (86%), 121/182 (67%) and 144/185 (78%) in the per protocol population respectively; 3.0 g OD was superior to both low‐dose regimens for the primary endpoint (i.e. P < 0.001, 3.0 g OD vs. 1.5 g OD; P = 0.024, 3.0 g OD vs. 0.5 g t.d.s.; superiority test, per protocol population). Safety analysis, including comprehensive renal monitoring, revealed no concern in any treatment group. Conclusion Mesalazine 3.0 g once daily was the most effective dose for maintenance of remission in ulcerative colitis of the three regimens assessed, with no penalty in terms of safety.     

Mesalamine in the treatment and maintenance of remission of ulcerative colitis

Ulcerative colitis (UC) is a chronic disease of the GI tract that is characterized by mucosal inflammation in the colon. Mesalamine (mesalazine) is a 5-aminosalicylic acid compound that is the first-line treatment for patients with mild-to-moderate UC. There are multiple formulations of mesalamine available, primarily differentiated by their means of delivering active mesalamine to the colon. Mesalamine has been demonstrated in randomized controlled trials to induce both clinical response and remission, and maintain clinical remission, in these patients. It has few serious adverse effects and is generally well tolerated by patients. The main areas of uncertainty with use of mesalamine in patients with UC center on the optimal dose for induction of response, how to maintain patient adherence and the role of mesalamine in cancer chemoprophylaxis. Generic forms of mesalamine have yet to be approved by regulatory bodies in the USA.     

Mesalamine in the treatment and maintenance of remission of ulcerative colitis

Ulcerative colitis (UC) is a chronic disease of the GI tract that is characterized by mucosal inflammation in the colon. Mesalamine (mesalazine) is a 5-aminosalicylic acid compound that is the first-line treatment for patients with mild-to-moderate UC. There are multiple formulations of mesalamine available, primarily differentiated by their means of delivering active mesalamine to the colon. Mesalamine has been demonstrated in randomized controlled trials to induce both clinical response and remission, and maintain clinical remission, in these patients. It has few serious adverse effects and is generally well tolerated by patients. The main areas of uncertainty with use of mesalamine in patients with UC center on the optimal dose for induction of response, how to maintain patient adherence and the role of mesalamine in cancer chemoprophylaxis. Generic forms of mesalamine have yet to be approved by regulatory bodies in the USA.     

Oral tobramycin in ulcerative colitis: effect on maintenance of remission

Oral tobramycin for 7 days has been shown to be of benefit as an adjunct to conventional medication in acute ulcerative colitis. Eighty-one patients (40 who had received tobramycin; 41 placebo) who had been enrolled in a double-blind placebo-controlled trial of this drug in acute disease were subsequently followed to determine whether this short-term benefit persisted. Relapse was defined as a liquid stool frequency of three times daily with rectal bleeding. Results were analysed by the log-rank test on Kaplan-Meier survival curves. Treatment failure was defined as a lack of response by the end of the acute trial period, or subsequent relapse. In a second analysis, only those entering remission at the end of the acute trial were considered, and followed to relapse. Although at the start of the follow-up period significantly fewer patients in the tobramycin group had failed (failed: tobramycin 9, placebo 24; not failed tobramycin 31; placebo 17;P= 0.001), the failure-free survival curves subsequently converged and did not differ significantly. After 1 and 2 years, the failure-free survival rates were 40% (S.E. = 7.8%) and 20% (S.E. = 6.3%) for the tobramycin group and 24% (S.E. = 6.7%) and 12% (S.E. = 5.1%) for the placebo group. When only those entering remission were considered, there was no significant difference in the relapse rates in the two groups. Benefit from tobramycin is therefore short-lived and may reflect short-term changes in the faecal flora.     

美沙拉嗪治疗溃疡性结肠炎的疗效

目的 探讨美沙拉嗪治疗溃疡性结肠炎的临床疗效与安全性.方法 溃疡性结肠炎患者84例随机均分为两组,分别在支持治疗的基础上,观察组加用美沙拉嗪治疗,每日口服3次,1.0 g/次;对照组加用柳氮磺胺吡啶常规治疗;疗程为8周.比较两组临床疗效和治疗前后外周血C反应蛋白(CRP)、IL-6和TNF-α变化,记录治疗期的不良反应.结果 观察组的总有效率为97.6％,明显高于对照组的81.0％ (P＜0.05).治疗后两组外周血CRP和炎性细胞因子IL6和TNF-α水平均明显下降,且观察组的改变更为明显(P＜0.05).两组的不良反应发生率相仿(4.8％vs.9.5％)(P＞0.05).结论 美沙拉嗪治疗溃疡性结肠炎的临床疗效优于柳氮磺胺吡啶,能够明显改善患者体内的炎性状态.     

Efficacy and safety of drugs for ulcerative colitis

Importance of the field: Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon that carries considerable burden and morbidity for patients and presents a constant challenge in management for gastroenterologists. Continued advances in medical therapies provide a range of treatment options for patients, but with this is the need to balance the potential benefits of a particular medication with its side effect profile in both the short and the long term.

Areas covered in this review: This article will review the current drugs used in the treatment of UC, including 5-amninosalicylates, antibiotics, steroids, immunomodulators and biologics, with particular attention to their indications, efficacy and toxicity profile.

What the reader will gain: The reader will gain a comprehensive understanding of the various medical therapies used in the treatment of UC with focus on efficacy and toxicity profiles, allowing providers to choose appropriate medical therapies for their patients.

Take home message: The particular agent used depends upon the extent and severity of disease, with mild-to-moderate disease treated with conventional therapy including 5-amninosalicylates. Steroids are used in the short term to bring active disease into remission, and the more aggressive immunomodulators and biologics are reserved for more severe disease given their toxicity profiles.