SELECTED SUMMARIES Infliximab Decreases Colectomy Rates in Moderate to Severe Ulcerative Colitis: Big News or Big Deal? Sandborn WJ, Rutgeerts P, Feagan BG, et al. Colectomy rate comparison after treatment of ulcerative colitis with placebo or infliximab. Gastroenterology. 2009;137:1250–1260. U lcerative colitis (UC) is a chronic relapsing and remit- ting inflammatory disorder of the colon that carries a 10-year cumulative risk for colectomy of 10%. 1 To date, no medical therapy has been proven to alter the natural his- tory of UC. Aminosalicylates and azathioprine are mainstays of therapy in UC. More recently, infliximab has been shown to induce and maintain remission in outpatients with moder- ate to severe disease. 2 In severe steroid-refractory disease, small studies suggest that infliximab and cyclosporine may prevent colectomy in the short-term, 3,4 although long-term outcomes have been disappointing. Colectomy rates have been demonstrated to be as high as 88% at 7 years after treat- ment with cyclosporine. 5 Colectomy rates in hospitalized steroid-refractory UC are equally unsatisfactory. 6 The Active Ulcerative Colitis Trials (ACT-1 and ACT-2) were randomized, double-blinded, placebo-con- trolled trials that evaluated the efficacy of infliximab in moderate to severely active UC. At the time of initial data publication, colectomy rates at 1 year were unavailable due to incomplete data and the need for continued long-term follow-up. 2 The current study by Sandborn et al presents the 54-week colectomy incidence from these trials. In ACT-1 and ACT-2, 728 patients with moderate to severe ulcerative colitis were randomized to intravenous infliximab 5 mg/kg or 10 mg/kg (n ¼ 242 in each group) or placebo (n ¼ 244) at weeks 0, 2, 6, and every 8 weeks thereafter through week 46 (ACT-1) or 22 (ACT-2). Patients were excluded if colectomy was likely or intrave- nous steroids were used in the prior 2 weeks. The primary outcome measure was response at week 8, with the inci- dence of colectomy a prespecified secondary outcome mea- sure. Existing colectomy follow-up data were augmented by an extension study (ACT-2 extension), the Remicade Safety Under Long-term Study in Ulcerative Colitis (RESULTS-UC), and a retrospective targeted poststudy fol- low-up. Taken together, 87% (630/728) of all patients had colectomy incidence data available for analysis. The cumulative incidence of colectomy through 54 weeks was 10% in the combined infliximab group (46/484) and 17% in the placebo group (36/244) (P ¼ 0.02), which resulted in an absolute risk reduction of 7% (95% confidence interval [CI] 0.01–0.12), a hazard ratio of 0.59, and an number needed to treat (NNT) of 14. Therefore, patients receiving infliximab were 41% less likely to undergo a colectomy at 54 weeks. Notably, while the incidence of colectomy was lower in those patients treated with infliximab, this difference reached statistical significance in only the 10 mg/kg group. Compared to placebo, fewer patients in the combined inflixi- mab-treated group were hospitalized for a UC-related event (20 versus 40/100 patient-years, P ¼ 0.003) or underwent a UC-related surgery/procedure (21 versus 34/100 patient years, P ¼ 0.03). However, this statistical difference again did not reach significance for UC-related surgery/procedures in the infliximab 5 mg/kg group (P ¼ 0.15). Adverse events occurred more frequently in the combined infliximab group (86%) when compared to placebo (86% versus 80%, P ¼ 0.05). As in previous studies, infections appeared to be more common with either dose of infliximab compared to placebo (i.e., tuber- culosis, histoplasmosis, herpes zoster), although this did not achieve statistical significance (P ¼ 0.06). There was no dif- ference between groups with regard to serious adverse events, serious infections, or discontinuation of drug due to an adverse event. Four patients treated with infliximab developed cancer compared to one patient receiving placebo, which was not a statistically significant difference. Factors predictive of colec- tomy, independent of treatment group, were center location in North America (P ¼ 0.05), corticosteroid use (P ¼ 0.01), C- reactive protein (CRP) 2(P ¼ 0.04), baseline Mayo score of 10–12 (P ¼ 0.01), duration of disease >3 years (P < 0.001), and treatment with placebo (P ¼ 0.05). COMMENT This long-term follow-up study by Sandborn et al is, to our knowledge, the first prospective study to demonstrate that a medical intervention can alter the need for colectomy in moderate-to-severe ulcerative colitis, an important finding in a DOI 10.1002/ibd.21498 Published online 5 November 2010 in Wiley Online Library (wileyonlinelibrary.com). Received for publication June 9, 2010; Accepted August 11, 2010. Copyright V C 2010 Crohn’s & Colitis Foundation of America, Inc. Inflamm Bowel Dis  Volume 17, Number 7, July 2011 1626