Treatment of choice for acute severe steroid-refractory ulcerative colitis is remicade.

U lcerative colitis (UC) is usually a lifelong chronic disease with remissions and exacerbations. A severe attack, a potentially fatal condition, is observed in 15% and is sometimes the first manifestation.1 Before the corticosteroid era a severe attack was associated with a mortality of about 30%.1 The introduction of corticosteroids sharply reduced the mortality2 and corticosteroids remain as a mainstay in the treatment of an acute attack of UC. The Oxford model, intensive intravenous treatment (IIVT) with high-dose corticosteroids and early colectomy in patients not responding within 5–7 days, reduced the mortality further. However, the colectomy rate remained high and 35%–40% of patients with a severe attack needed surgery in the short term.3,4 Proctocolectomy essentially cures the patients with UC, but reconstructive surgery, such as an ileo-pelvic pouch (IPAA), is often associated with complications such as pouchitis, reduced fecundity, and quality of life compared with colon-sparing measures.5 This led to the search for therapeutic alternatives in patients not responding to IIVT. The importance of achieving remission is underscored by the fact that the long-term colectomy rate in patients with a severe attack who achieve clinical and endoscopic remission after IIVT is similar to those with a moderately severe or mild attack.6 Intravenous cyclosporine-A (CsA) was the first successful rescue therapy, showing an impressive initial response in a small randomized trial. Twenty patients not responding to 7 days of intravenous (i.v.) corticosteroid treatment, equivalent to a daily dose of 300 mg of hydrocortisone, were included. Nine of 11 patients treated with i.v. CsA (4 mg/kg) in comparison to none of 9 patients in the placebo group responded and achieved the primary endpoint; a decline in the Lichtiger index to less than 10 on 2 consecutive days.7 Since then, several retrospective analyses from referral centers have shown that about 75%–80% of the patients respond to CsA,8–10 although the evidence is limited.11 Yet the long-term results appear disappointing. Sixty-five percent of the patients have been reported to relapse within the first year8 and the vast majority undergo colectomy in the long run. Retrospective studies from tertiary centers within Europe have shown that 68%–88% of patients treated with CsA for severe UC had a colectomy within 7 years.8,9 These results are difficult to evaluate due to the lack of controlled trials. However, the high relapse and colectomy rate questions whether the patients treated with CsA really achieved remission or if only partial improvement occurred. In our series less than 35% of patients with severe UC who achieved clinical and endoscopic remission when treated with IIVT relapsed within the first year.6 Furthermore, the colectomy rate and relapse incidence in the period beyond 3 months up to 20 years after IIVT was not influenced by the severity of the index attack, except for a lower relapse incidence after a severe attack.6 Treatment with CsA is associated with adverse events, such as seizure, paresthesia, hypertension, hypertrichiosis, nephrotoxicity, infectious complications as well as a significant mortality. Deaths have been reported in 2.8%–3.5% of patients treated at some referral centers.9,12 Treatment with a lower dose, 2 mg/kg, might reduce the risk of side effects,10 but CsA treatment still requires continuous parenteral administration and careful laboratory monitoring. Any hypomagnesemia or hypocholesterolemia need correction before treatment. The toxicity profile also underlines the importance of keeping the i.v. treatment period as short as possible. The optimal strategy for this, including the possible role of other immune-modulating agents in combination with CsA, has yet to be defined. Usually patients responding to i.v. CsA are switched to oral cyclosporine for 3 months while steroids are tapered and the maintenance effect of azathioprine or 6-mercaptopurine achieved. There has been a rapid development in the use of biologics in the treatment of inflammatory bowel disease during the last decade. Infliximab (IFX) (Remicade, Centocor, Malvern, PA), a chimeric monoclonal immunoglobulin G1 antibody toward tumor necrosis factor alpha (TNF), was the first drug. Initial studies focused on Crohn’s disease, believed to be a typical Th1-type of disease, driven by ThReceived for publication November 27, 2007; Accepted September 4, 2008. From the Division of Gastroenterology, Department of Internal Medicine, Örebro University Hospital, Sweden. Reprints: Jonas Halfvarson, Division of Gastroenterology, Department of Internal Medicine, Örebro University Hospital, Örebro, Sweden (e-mail: jonas.halfvarson@orebroll.se). Copyright © 2008 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1002/ibd.20782 Published online 22 October 2008 in Wiley InterScience (www.interscience. wiley.com).