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.     

Review article: balsalazide therapy in ulcerative colitis

Balsalazide is a 5-aminosalicylic acid (mesalazine) pro-drug which has an inert carrier molecule instead of the sulfapyridine moiety of sulfasalazine. It is designed to deliver 5-aminosalicylic acid to the colonic mucosa without the sulfapyridine-associated side-effects encountered with sulfasalazine. Several studies have confirmed the efficacy and patient tolerance of balsalazide. When compared to mesalazine at equivalent doses, it induced symptomatic and complete remission of acute ulcerative colitis in a greater proportion of patients. In particular, patients with resistant left-sided disease were shown to have a higher probability of achieving remission. Balsalazide was beneficial in patients with troublesome nocturnal symptoms. It has a similar efficacy in maintaining remission when compared to sulfasalazine and mesalazine. The advantage of balsalazide over other 5-aminosalicylic acid compounds is its superior patient tolerability with minimal side-effects.     

MMX mesalazine for the induction of remission of mild-to-moderately active ulcerative colitis: efficacy and tolerability in specific patient subpopulations

Background  Two phase III studies have evaluated mesalazine (mesalamine) with MMX (Multi Matrix System) technology in patients with active mild-to-moderate ulcerative colitis.
Aim  To determine the efficacy of MMX mesalazine for the induction of clinical and endoscopic remission in specific subgroups of patients with active, mild-to-moderate ulcerative colitis.
Methods  Data from two double-blind, placebo-controlled trials were analysed (517 out-patients). Patients were randomized to receive MMX mesalazine [2.4 g/day (once daily or 1.2 g twice daily) or 4.8 g/day (once daily)] or placebo for 8 weeks.
Results  The percentages of patients treated with MMX mesalazine, 2.4 or 4.8 g/day, in clinical and endoscopic remission at week 8 were similar and significantly ( P  < 0.05) greater than placebo in subgroups stratified by disease extent, disease severity and gender and among patients not previously receiving low-dose 5-aminosalicylic acid. Among patients transferring directly from prior low-dose oral 5-aminosalicylic acid, MMX mesalazine 4.8 g/day was significantly ( P  = 0.018) more effective than placebo in inducing clinical and endoscopic remission. Efficacy over placebo did not reach significance in patients transferring directly to MMX mesalazine 2.4 g/day.
Conclusion  MMX mesalazine is effective in active UC regardless of disease extent, disease severity, gender and previous, low-dose, 5-ASA therapy.     

Review article: the long-term management of ulcerative colitis

After the induction of remission, the second priority of therapy for ulcerative colitis is sustained clinical remission, defined as the absence of inflammatory symptoms (diarrhoea, bleeding, rectal urgency) and the maintenance of an intact mucosa, with the absence of ulcers, friability or significant granularity at endoscopy. The 'optimal' maintenance strategy will depend on the therapy needed to induce remission. Thus, the transition from induction to maintenance therapy will be determined by the intensity of acute therapy necessary to induce remission and the duration of therapy required to complete the resolution of clinical symptoms. There are few controlled clinical trials pertaining to maintenance after each induction regimen. However, experience dictates that aminosalicylates are efficacious after aminosalicylate-induced remissions, that steroids should be tapered according to the time required to induce remission, that patients requiring ciclosporin will benefit from the addition of long-term immunomodulation with azathioprine or mercaptopurine, and that many patients with distal colitis who require topical mesalazine (mesalamine) will continue to need topical therapy to maintain remission, albeit at reduced frequency. The expectations for maintenance therapy require patient adherence to the prescribed treatment regimen. Patients require education with regard to the long-term goals of maintenance therapy (e.g. prevention of relapse, reduction of long-term complications of disease activity or risks of acute therapy with steroids), and should be warned against the use of nonsteroidal anti-inflammatory drugs and cautioned about the cessation of smoking, when applicable, due to potential risks of relapse or chronic activity.     

美沙拉嗪口服联合灌肠治疗溃疡性结肠炎120例疗效观察

目的观察美沙拉嗪口服联合灌肠治疗溃疡性结肠炎的疗效。方法选择240例轻、中度溃疡性结肠炎患者,随机分为两组:治疗组120例予口服美沙拉嗪,1.0g/次,3次/d,同时给予美沙拉嗪灌肠剂(莎尔福灌肠剂,4g/60ml,用时稀释到100ml)4g/100ml,1次/晚,保留灌肠,8周为1疗程;对照组120例,予口服柳氮磺吡啶片(Alicylazosulfapyridine,SASP)1.0g,4次/d。疗程为8周。结果治疗8周后,治疗组显效率和总有效率明显优于对照组,差异有统计学意义(P<0.05);两组均有不良反应的发生,治疗组发生13例,发生率10.8%,对照组发生68例,发生率56.7%,治疗组明显低于对照组,差异有统计学意义(P<0.05)。结论美沙拉嗪了治疗溃疡性结肠炎临床疗效显著,且不良反应小。     

Review article: Immunosuppressants in distal ulcerative colitis

BACKGROUND: Distal ulcerative colitis may prove to be resistant to steroids and aminosalicylates, but total colectomy is more difficult to justify than in severe extensive colitis. Immunosuppression is of established benefit in generalized colitis, but there are no data available specific to distal disease. AIM: To determine whether the protocol-driven use of immunosuppressants in resistant distal ulcerative colitis is of similar efficacy and safety to that in extensive disease. METHODS: Two hundred and twenty-eight patients with distal ulcerative colitis seen in a 5-year period were identified from a prospective database. Details of 52 who had received immunosuppression were analysed. RESULTS: The 52 patients received 68 courses of therapy (53 azathioprine, five mercaptopurine, 10 ciclosporin). The thiopurines yielded clinically valuable responses in only 43% of courses, with failure of response in 16% and toxicity in 34%. Ciclosporin was helpful on only two of 10 occasions. Eight patients required total colectomy. Adverse events were typical of those normally associated with immunosuppressants, with potential risk to life in seven patients; treatment was discontinued because of toxicity on a total of 31% of occasions. CONCLUSIONS: Immunosuppression appears to be of lower efficacy and higher toxicity in resistant distal colitis than when used in more extensive colitis.     

Review article: monitoring activity in ulcerative colitis

The monitoring of patients with ulcerative colitis is easier than in patients with Crohn's disease for several reasons: the severity of symptoms and activity of inflammation tend to run parallel in ulcerative colitis when involvement of the large bowel is more extensive. The easy accessibility of the colonic mucosa by endoscopic and histologic examination provides further information concerning the degree of inflammation. In severe attacks, the patient must be admitted to hospital and monitored carefully. Clinical and laboratory parameters (such as daily stools, CRP, fever, haemoglobin, albumin, etc.) and plain abdominal X-ray are useful in monitoring the activity of the disease and to predict the outcome. In mild to moderate attacks, endoscopic and histologic evaluation are the best methods for choosing the appropriate treatment and for assessing response.     

Review article: medication non-adherence in ulcerative colitis--strategies to improve adherence with mesalazine and other maintenance therapies

Background  Significant number of patients with ulcerative colitis (UC) fail to comply with treatment.
Aims  To review issues surrounding medication non-adherence in inflammatory bowel disease (IBD), including the clinical and health service implications in the UK, and discuss strategies for optimizing medication adherence.
Methods  Articles cited were identified via a PubMed search, utilizing the words IBD, adherence, compliance, medication and UC.
Results  Medication non-adherence is multifactorial involving factors other than dosing frequency. Male gender (OR: 2.06), new patient status (OR: 2.14), work and travel pressures (OR: 4.9) and shorter disease duration (OR: 2.1), among others are proven predictors of non-adherence in UC. These indicators can identify 'at-risk' patients and allow an individually tailored treatment approach to be introduced that optimizes medication adherence. A collaborative relationship between physician and patient is important; several strategies for improving adherence have been proven effective including open dialogue that takes into consideration the patient's health beliefs and concerns, providing educational (e.g. verbal/written information, self-management programmes) and behavioural interventions (e.g. calendar blister packs, cues/reminders).
Conclusions  Educational and behavioural interventions tailored to individual patients can optimize medication adherence. Additional studies combining educational and behavioural interventions may provide further strategies for improving medication adherence rates in UC.