Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 2: Current Management

Abstract

The treatment strategy for ulcerative colitis [UC] is mainly based on the severity, distribution [proctitis, left-sided, extensive]1 and pattern of disease. The latter includes relapse frequency, disease course, response to previous medications, side effects of medication, and extra-intestinal manifestations. Age at onset, and disease duration are also important factors. It is important to distinguish patients with severe UC necessitating hospital admission from those with mild or moderately active disease who can be managed as outpatients. The best validated and most widely used index for identifying severe UC remains that of Truelove and Witts.2 Patients with bloody stool frequency ≥ 6/day and a tachycardia [> 90 min−1], or temperature > 37.8°C, or anaemia [haemoglobin < 10.5 g/dl], or an elevated erythrocyte sedimentation rate [ESR] [> 30 mm/h] have severe UC. Only one additional criterion in addition to the bloody stool frequency ≥ 6/day is needed to define a severe attack.3,4 In practice, a C-reactive protein [CRP] of 30 mg/l can be substituted for the ESR. A mesalamine 1-g suppository once daily is the preferred initial treatment for mild or moderately active proctitis [EL1]. Mesalamine foam or enemas are an alternative [EL1], but suppositories deliver the drug more effectively to the rectum and are better tolerated [EL3]. Topical mesalamine is more effective than topical steroids [EL1]. Combining topical mesalamine with oral mesalamine or topical steroids is more effective [EL2] Refractory proctitis may require treatment with systemic steroids, immunosuppressants, and/or biologics [EL4] Topical mesalamine [5-aminosalicylic acid or 5-ASA] is the first-line therapy for proctitis. A Cochrane systematic review of 38 clinical trials of treatment of proctitis and left-sided colitis confirmed its superiority over placebo for inducing symptomatic, endoscopic, histological response and remission.5 The pooled odds ratio [OR] was: 8.3 for symptomatic remission (8 trials, 95% confidence interval [CI] 4.28–16.12; p < 0.00001); 5.3 for endoscopic remission [7 trials, 95% CI 3.15–8.92; p < 0.00001]; and 6.3 for histological remission [5 trials, 95% CI 2.74–14.40; p < 0.0001]. Suppositories are more appropriate than enemas in proctitis as they better target the site of inflammation and are more acceptable for patients.6 There is no dose response for topical therapy above a dose of 1 g 5-ASA daily.5,7 Once-daily topical therapy is as effective as divided doses.8,9 A meta-analysis found no difference between oral and topical 5-ASA for induction of remission (risk ratio [RR] for no remission with topical 5-ASA: 0.82, 95% CI 0.52–1.28) or time to remission [24.8 vs 25.5 days, respectively], but the trials included in this meta-analysis enrolled patients with UC of any extent, not specifically proctitis.10 In the single trial that included only patients with proctitis, rectal 5-ASA was more effective than oral 5-ASA alone.11 However, if oral 5-ASA is used alone, 3.6 g of a pH-dependent release preparation appears to be more effective than lower doses or placebo.12 Moreover in patients with proctosigmoiditis, 5-ASA granules rather than tablets are more likely to obtain clinical [78% vs 55%, p < 0.001] and endoscopic [67% vs 43%, p < 0.001] remission.13 The combination of oral and topical 5-ASA is more effective than either alone in patients with disease extending < 50 cm from the anal verge,14 although there is no trial of combination therapy for proctitis alone. Combining topical 5-ASA and topical steroids also helps: beclomethasone dipropionate [3 mg] and 5-ASA [2 g] enemas produced significantly better clinical, endoscopic, and histological improvement than either agent alone.15 Two meta-analyses have shown that topical 5-ASA is more effective than topical steroids, whether assessing symptomatic, endoscopic, or histological remission.16 Consequently topical steroids be to patients who have an or who are to topical A trial shown that g rectal foam alone is more than placebo in inducing remission at in patients with mild to vs p < drug not with topical and endoscopic be confirmed in those with to with oral topical 5-ASA and/or topical Refractory proctitis may require treatment with systemic steroids, or The of proctitis is in to moderately active left-sided ulcerative colitis be with an ≥ 1 with oral mesalamine ≥ [EL1], is more effective than oral or topical or topical steroids alone [EL1]. Topical mesalamine is more effective than topical steroids [EL1]. Once-daily with mesalamine is as effective as divided doses are appropriate in patients with to severe and in those with mild who not to mesalamine [EL1]. beclomethasone dipropionate and as oral in patients with mild to moderately active ulcerative colitis can be in patients with mild to disease who are or to left-sided colitis is an for hospital admission oral and topical 5-ASA is the first-line therapy for mild to moderately active left-sided with an of to remission o