Current management of severe ulcerative colitis

Approximately 15% of patients with ulcerative colitis develop an acute attack of severe colitis, and 30% of these patients require colectomy. Severe ulcerative colitis is therefore considered a medical emergency, the management of which requires close collaboration between gastroenterologists and surgeons. The mortality rate for patients with severe ulcerative colitis is now <1% in specialist centers, but it was high before intravenous steroid therapy and early surgery were introduced; indeed, mortality is still high in nonspecialized centers. As colectomy severely affects quality of life, therapy with intravenous ciclosporin and, more recently, infliximab has been introduced to try to avoid the need for surgery. Ciclosporin induces short-term remission, but the long-term benefit remains unsatisfactory as colectomy is often only delayed. A significant short-term reduction in the colectomy rate has, however, been observed after infliximab treatment. The use of infliximab versus ciclosporin in patients with severe ulcerative colitis remains to be defined. The timing of surgery remains a cardinal decision in the management of severe ulcerative colitis; increased morbidity resulting from prolonged ineffective medical treatment and, therefore, a delay in surgical treatment should be avoided.     

Management of acute severe ulcerative colitis

Acute severe ulcerative colitis is a potentially lethal condition that requires a pro-active approach with either effective medical treatment or timely colectomy. Although intravenous corticosteroids remain the first line treatment, in patients not responding after 3-5 days rescue medical therapy with either intravenous (IV) cyclosporine 2 mg/kg or infliximab 5 mg/kg IV should be considered. Controlled evidence supports the use of both treatments but medical rescue therapy should not defer the decision for colectomy in patients with inadequate response. Providing clear guidance for the choice between both agents is impossible due to the lack of comparative trials. The better short-term safety profile and the option for maintenance treatment favour infliximab specifically in patients already exposed to immunosuppressives. The rapid onset of action and the short half-life are advantages of cyclosporine in patients with imminent risk of colectomy. Even if cyclosporine and probably also infliximab only postpone colectomy in at least half of the patients, elective colectomy in a later stage of the disease may offer better outcomes. Whereas prolonged exposure to steroids predisposes to an increased rate of peri-operative complications it is still debated whether cyclosporine or infliximab increase peri-operative morbidity in ulcerative colitis.     

Predicting outcome in severe ulcerative colitis.

BACKGROUND: Simple criteria are needed to predict which patients with severe ulcerative colitis will respond poorly to intensive medical treatment and require colectomy. AIMS: To find out if the early pattern of change in inflammatory markers or other variables could predict the need for surgery and to evaluate the outcome of medical treatment during one year follow up. PATIENTS: 51 consecutive episodes of severe colitis (Truelove and Witts criteria) affecting 49 patients admitted to John Radcliffe Hospital, Oxford. METHODS: Prospective study monitoring 36 clinical, laboratory, and radiographic variables. All episodes treated with intravenous and rectal hydrocortisone and 14 of 51 with cyclosporine. RESULTS: Complete response in 21 episodes (< or = 3 stools on day 7, without visible blood), incomplete response in 15 (> 3 stools or visible blood on day 7, but no colectomy), and colectomy on that admission in 15. During the first five days, stool frequency and C reactive protein (CRP) distinguished between outcomes (p < 0.00625, corrected for multiple comparisons) irrespective of whether patients or the number of episodes were analysed. It could be predicted on day 3, that 85% of patients with more than eight stools on that day, or a stool frequency between three and eight together with a CRP > 45 mg/l, would require colectomy. For patients given cyclosporine, four of 14 avoided colectomy but two continued to have symptoms. After admission, complete responders remained in remission for a median nine months and had a 5% chance of colectomy. Incomplete responders had a 60% chance of continuous symptoms and 40% chance of colectomy. CONCLUSIONS: After three days intensive treatment, patients with frequent stools (> 8/day), or raised CRP (> 45 mg/l) need to be identified, as most will require colectomy on that admission. The role of cyclosporine for treating severe colitis has yet to be defined. After seven days' treatment, patients with > 3 stools/day of visible blood have a 60% chance of continuous symptoms and 40% chance of colectomy in the following months.     

Colectomy rate in acute severe ulcerative colitis in the infliximab era

BACKGROUND: Severe ulcerative colitis is a potentially life-threatening condition. Due to advances in medical therapy, the mortality rate has dropped to <2% over the past 30 years, but the colectomy rate reaches 30%. Recently, infliximab has been shown to be effective as rescue therapy but little is known about long-term benefits. AIM: To evaluate short-and long-term colectomy rates for severe ulcerative colitis in the era of biological treatment and to identify predictive factors of long-term colectomy. PATIENTS AND METHODS: From 2001 to 2006 all in-patients with severe ulcerative colitis, according to Truelove and Witts criteria, were retrospectively reviewed. All patients had received intravenous steroid treatment; infliximab (5 mg/kg at 0, 2 and 6 weeks) was used as rescue therapy in steroid-refractory patients; colectomy was performed in patients who deteriorated whilst on steroid treatment or failed to respond to infliximab. RESULTS: Of the 314 ulcerative colitis patients hospitalized during the study period, 52 (16.5%) met the criteria of severe ulcerative colitis. After median 7 days (range 4-15) on intravenous steroids, 37/52 (71%) patients showed a clinical response, while 15/52 (29%) were steroid-refractory. Of these, four underwent urgent colectomy and 11 received infliximab. A clinical response was observed in all infliximab-treated patients. In the long-term, another six patients underwent elective colectomy. The overall colectomy rate, following the acute attack, was 19%; the cumulative probability of a course without colectomy was 90%, 86%, 84%, 81%, after 6, 12, 18 and 24 months, respectively. No deaths occurred. The long-term colectomy risk was comparable in patients treated with infliximab and in steroid-responsive patients (18% vs. 11% respectively; OR 1.9; 95% CI 0.26-14.5). No predictive factors of colectomy, in the long-term, were identified. CONCLUSIONS: Surgery continues to play an important role in acute severe ulcerative colitis. Infliximab can avoid urgent colectomy in steroid-refractory patients but the risk of elective colectomy, in the long-term, is not modified.     

Treatment of severe steroid refractory ulcerative colitis

Although systemic steroids are highly efficacious in ulcerative colitis （UC）, failure to respond to steroids still poses an important challenge to the surgeon and physician alike. Even if the life time risk of a fulminant UC flare is only 20%, this condition is potentially life threatening and should be managed in hospital. If patients fail 3 to 5 d of intravenous corticosteroids and optimal supportive care, they should be considered for any of three options： intravenous cyclosporine （2 mg/kg for 7 d, and serum level controlled）, infliximab （5 mg/kg Ⅳ, 0-2-6 wk） or total colectomy. The choice between these three options is a medicalsurgical decision based on clinical signs, radiological and endoscopic findings and blood analysis （CRP, serum albumin）. Between 65 and 85% of patients will initially respond to cyclosporine and avoid colectomy on the short term. Over 5 years only 50% of initial responders avoid colectomy and outcomes are better in patients naive to azathioprine （bridging strategy）. The data on infliximab as a medical rescue in fulminant colitis are more limited although the efficacy of this anti tumor necrosis factor （TNF） monoclonal antibody has been demonstrated in a controlled trial. Controlled data on the comparative efficacy of cyclosporine and infliximab are not available at this moment. Both drugs are immunosuppressants and are used in combination with steroids and azathioprine, which infers a risk of serious, even fatal, opportunistic infections. Therefore, patients not responding to these agents within 5-7 d should be considered for colectomy and responders should be closely monitored for infections.     

Management of acute severe ulcerative colitis

The management strategy of acute severe ulcerative colitis has evolved over the past decade from being entirely restricted to twin choices of intravenous steroids or colectomy to include colon rescue therapies like cyclosporin as well as infliximab. However it still remains a medical emergency requiring hospitalization and requires care from a multidisciplinary team comprising of a gastroenterologist and a colorectal surgeon. The frame shift in management has been the emphasis on time bound decision making with an attempt to curtail the mortality rate to below 1%. Intravenous corticosteroids are the mainstay of therapy. Response to steroids should be assessed at day 3 of admission and partial/non-responders should be considered for alternative medical therapy/surgery. Medical rescue therapies include intravenous cyclosporin and infliximab. Cyclosporin is administered in a dose of 2 mg/kg per day and infliximab is administered as a single dose intravenous infusion of 5 mg/kg. Approximately 75% patients have short term and 50% patients have long term response to cyclosporin. Long term response to cyclosporin is improved in patients who are thiopurine naïve and are started on thiopurines on day 7. Infliximab also has a response rate of approximately 70% in short term and 50% in long term. Both cyclosporin and infliximab are equally efficacious medical rescue therapies as demonstrated in a recent randomized control trial. Patients not responding to infliximab or cyclosporin should be considered for colectomy.     

Infliximab efficacy in pediatric ulcerative colitis

BACKGROUND: The effects of infliximab, a tumor necrosis factor-alpha (TNF-alpha) antibody, have been well established in adult patients with inflammatory and fistulizing Crohn's disease. This study evaluates short- and long-term efficacy of infliximab in children with ulcerative colitis. METHODS: All pediatric patients with ulcerative colitis who received infliximab between July 2001 and November 2003 at the Johns Hopkins Children's Center were identified. Short- and long-term outcomes and adverse reactions were evaluated. RESULTS: Twelve pediatric patients with ulcerative colitis received infliximab for treatment of fulminant colitis (3 patients), acute exacerbation of colitis (3), steroid-dependent colitis (5), and steroid-refractory colitis (1). Nine patients had a complete short-term response, and 3 had partial improvement. The mean per patient dose of corticosteroid after the first infliximab infusion decreased from 45 mg/day at the first infusion to 22.2 mg/day at 4 weeks (P = 0.02) and 7.8 mg/day at 8 weeks (P = 0.008). Eight patients were classified as long-term responders with a median follow-up time of 10.4 months. Of the 4 long-term nonresponders, 3 underwent colectomy, and the fourth has ongoing chronic symptoms. Three of 4 long-term nonresponders were steroid-refractory compared with 1 of 8 long-term responders. Patients receiving 6-mercaptopurine had a better response to infliximab. CONCLUSION: Infliximab should be considered in the treatment of children with symptoms of acute moderate to severe ulcerative colitis.     

Severe ulcerative colitis： At what point should we define resistance to steroids？

Corticoesteroids are still the first-line treatment for active ulcerative colitis more than 50 years after the publication of trials assessing their beneficial effect, with about a 50% remission rate in cases of severe disease. The mortality related to severe attacks of ulcerative colitis has decreased dramatically, to less than 1%, in experienced centers, due to the appropriate use of intensive therapeutic measures （intravenous steroids, fluids and electrolytes, artificial nutritional support, antibiotics, etc）, along with timely decision-making about second-line medical therapy and early identification of patients requiring colectomy. One of the most difficult decisions in the management of severe ulcerative colitis is knowing for how long corticosteroids should be administered before deciding that a patient is a non-responder. Studies assessing the outcome of acute attacks after steroid initiation have demonstrated that, in steroid-sensitive patients, the response generally occurs early on, in the first days of treatment. Different indexes to predict treatment failure, when applied on the third day of treatment, have demonstrated a high positive predictive value for colectomy. In contrast to this resolute approach, which is the most widely accepted, other authors have suggested that in some patients a complete and prolonged response to steroids may take longer. Either way, physicians taking care of these patients need to recognize that severe ulcerative colitis may be life-threatening, and they need to be careful with excessively prolonged medical treatment and delayed surgery.     

Does Infliximab Influence Surgical Morbidity of Ileal Pouch-Anal Anastomosis in Patients with Ulcerative Colitis?

Purpose Since infliximab has been approved for treatment of patients with refractory ulcerative colitis, surgeons will be increasingly faced with operating on patients who have failed therapy with this potent immunosuppressant. This study was designed to compare short-term complications in patients with ulcerative colitis who were treated with and without infliximab before colectomy. Methods The charts of patients undergoing ileal pouch-anal anastomosis or subtotal colectomy for refractory ulcerative colitis during the five-year period ending October 2005 were reviewed. Postoperative medical and surgical complications were assessed. Results Seventeen patients had failed infliximab treatment and 134 patients were never treated with infliximab. Ileal pouch-anal anastomosis was performed in 112 patients (74 percent) and subtotal colectomy in 39 patients (36 percent). There were no deaths. Postoperative complications were observed in 43 patients (28 percent), with no significant difference observed between infliximab-treated (37 percent) and infliximab-untreated patients (27 percent). Of 61 patients (40 percent) treated with preoperative cyclosporine A, 5 patients also had been treated with infliximab. The infliximab and cyclosporine A-treated patient group had an 80 percent complication rate, significantly higher than the 29 percent complication rate noted in the cyclosporine A only-treated group (P = 0.04). Conclusions Although preoperative treatment with infliximab alone does not significantly increase the incidence of postoperative complications, using both inflixiamb and cyclosporine A before colectomy in refractory ulcerative colitis is associated with high surgical morbidity. Read at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 3 to 7, 2006. Reprints are not available.     

Granulocyte, macrophage, monocyte apheresis for refractory ulcerative proctitis

Refractory ulcerative colitis that fails conventional intense medical treatment often leads to colectomy. Although ciclosporin and infliximab may avert colectomy in certain cases, these treatments come with substantial toxicity and may only act as a bridge to avert emergency surgery. Granulocyte monocyte/macrophage adsorption apheresis is a new treatment and has shown efficacy for refractory colitis in up to 80% of cases in a Japanese study and is apparently only associated with negligible side effects. We report a case of severe refractory proctitis destined for colectomy effectively treated with granulocyte monocyte/macrophage adsorption apheresis. After two of five sessions the patient achieved full clinical remission, which has been sustained with the addition of azathioprine for more than 1 year.     

Steroid-refractory severe ulcerative colitis responding to cyclosporine and long-term follow-up

We report a case of steroid-refractory ulcerative colitis, treated with cyclosporine, in a 38-year-old woman with a 13-year history of ulcerative colitis. No remission was achieved with treatments that included intravenous hyperalimentation, sulfasalazine, and intensive parenteral prednisolone therapy for 4 weeks. Intravenous infusion of cyclosporine was performed because the patient refused to undergo surgery. Her condition improved dramatically and colectomy was avoided. She has been maintained on oral cyclosporine and azathioprine since steroids were discontinued, and she has remained in clinical and endoscopic remission for 2 years. The side effects were not significant, but mild paresthesia in both hands and mild hypertension, which was controlled by anti-hypertensives. Cyclosporine seems to be an effective treatment for patients with steroid-refractory severe active ulcerative colitis in whom colectomy seems inevitable. We believe further clinical trials of the treatment are warranted. (Received July 25, 1997; accepted Nov. 28, 1997)     

Infliximab for treatment of steroid-refractory ulcerative colitis

BACKGROUND: Success achieved in two subtypes of Crohn's disease has persuaded a few investigators to experiment the monoclonal anti-tumour necrosis factor antibody infliximab in the treatment of ulcerative colitis. So far, however, the results (achieved in some 30 steroid-refractory patients included in two independent full-papers) indicate a rate of initial response of 50% and of remission of 25%. AIMS: To analyse data of an open trial conducted on consecutive steroid-refractory severely ill patients admitted to our referral Unit. PATIENTS AND METHODS: In 9 months, infliximab was given to 8 patients (4 male, 4 female aged 20-60 years) with uncontrolled ulcerative colitis of whom 6 were non-responders to parenteral steroids. All received the first infliximab dose as an intravenous infusion of 5 mg/kg. RESULTS: Of the 8, 4 (50%) did not respond to the first injection and were submitted to urgent colectomy; the other four responded clinically. Two have maintained clinical remission for 7 months, without the need for steroids; both have received daily azathioprine at 2 mg/kg, and only one has received two further infliximab injections. Of the other two, one received a second injection at week 5, despite this relapsed, and underwent elective colectomy at that time; the other relapsed at 6 months and showed a partial response to a repeat infliximab infusion. Thus, the rate of sustained response is 2/8 (25%) in this study. CONCLUSION: These results, achieved in an open uncontrolled fashion, seem to reflect those of other independent studies. In our opinion, these findings warrant an in-depth reappraisal of the indication to use infliximab as rescue treatment for refractory ulcerative colitis.     

Infliximab to treat severe ulcerative colitis

A 48-year-old female with severe ulcerative colitis refractory to conventional therapy was referred to our facility for management. The patient showed extensive ulcerative colitis since the age of 20 years and had failed therapy with 5-aminosalicylic acid agents and azathioprine. The disease remained active despite treatment with steroids and cyclosporine. The clinical and endoscopic parameters were consistent with severe disease. Infectious precipitants were ruled out. Given the severity of the disease and in order to avoid a colectomy, we started the patient on infliximab therapy. A dramatic clinical and endoscopic response was observed and she remained in remission at the end of a 1-year follow-up period. We discuss findings in the literature regarding the use of infliximab therapy in patients with ulcerative colitis who have failed steroids and cyclosporine.     

Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study

BACKGROUND & AIMS: Despite treatment with corticosteroids, severe to moderately severe attacks of ulcerative colitis have a high colectomy rate. We intended to find a rescue therapy other than cyclosporin A, which imposes a high risk of side effects and cyclosporine-related mortality. METHODS: This was a randomized double-blind trial of infliximab or placebo in severe to moderately severe ulcerative colitis not responding to conventional treatment. Patients were randomized to infliximab/placebo either on day 4 after the initiation of corticosteroid treatment if they fulfilled the index criteria for fulminant ulcerative colitis on day 3 or on day 6-8 if they fulfilled index criteria on day 5-7 for a severe or moderately severe acute attack of ulcerative colitis. Results were analyzed according to the intention-to-treat principle. The primary end point was colectomy or death 3 months after randomization. Secondary end points were clinical and endoscopic remission at that time in patients who did not undergo operation. RESULTS: Forty-five patients were included (24 infliximab and 21 placebo). No patient died. Seven patients in the infliximab group and 14 in the placebo group had a colectomy (P = .017; odds ratio, 4.9; 95% confidence interval, 1.4-17) within 3 months after randomization. No serious side effects occurred. Three patients in the placebo group required operation for septic complications. CONCLUSIONS: Infliximab 4-5 mg/kg is an effective and safe rescue therapy in patients experiencing an acute severe or moderately severe attack of ulcerative colitis not responding to conventional treatment.     

Outcomes out to 12 months after sequential use of high-dose tofacitinib following infliximab in acute severe ulcerative colitis

Acute severe colitis (ASUC) remains a significant cause of morbidity in up to 25% of patients with ulcerative colitis during their disease course. We present the outcomes out to 12 months following the use of high-dose tofacitinib, 10 mg three times daily (TDS), in patients with steroid and infliximab refractory ASUC. A total of 11 patients with ASUC who were treated with high-dose tofacitinib after failing sequential infliximab therapy between 2019 and 2021 were identified at an Australian tertiary centre. Ten of 11 patients demonstrated clinical and biochemical response to treatment during admission. Two of 11 patients required colectomy, one during the index admission and the other during re-admission 10 days after the index presentation. Nine of the initial responders had a median Mayo score of 1 (IQR 0–4) at both 6 and 12 months, and all remained colectomy-free out to 12 months. Neither venous thromboembolic events nor major infective complications were observed. Tofacitinib may be a safe and effective induction and maintenance agent in the treatment of steroid and infliximab refractory ASUC. Prospective studies with long-term follow-up are required to explore the use of tofacitinib in ASUC before it can be routinely recommended as salvage therapy.     

Prognosis of severe attacks in ulcerative colitis: effect of intensive medical treatment

BACKGROUND: Severe attacks of ulcerative colitis have a high risk of colectomy. AIMS: To evaluate the effects of standard medical management and to identify the clinical and laboratory variables capable of predicting the clinical outcome. MATERIALS AND METHODS: Prospective study monitoring the clinical and laboratory variables in 67 patients with severe colitis. Therapy consisted of prednisone, cyclosporin if no response, and azathioprine for maintenance. End-points were colectomy or remission. Logistic regression analysis was applied for statistical evaluation. RESULTS: Fourteen (20%) patients required colectomy, 34 (50%) patients achieved remission with steroids, 25 (37%) patients received cyclosporin, 19 (76%) with benefit. Increased body temperature, pulse rate, sedimentation rate and C-reactive protein levels on admission were significantly associated with colectomy. Sedimentation rate greater than 75 mm/h and body temperature exceeding 38 degrees C at admission had 4.6- and 8.8-fold increased risk of colectomy. Less than 40% reduction in the bowel movements within 5 days predicted no response to steroids. Azathioprine maintained remission in 70% of the patients. CONCLUSIONS: Elevated sedimentation rate and fever at day 1 best predict colectomy in severe colitis. Less than 40% reduction in the bowel movements at day 5 predicts no response to steroids. Cyclosporin has a high rate of success in acute attacks and azathioprine in maintaining remission.     

Do patient preferences influence decisions on treatment for patients with steroid-refractory ulcerative colitis?

BACKGROUND & AIMS: Patients with steroid-refractory ulcerative colitis face a difficult treatment decision between colectomy and therapy with infliximab or cyclosporine. The aim of this study was to understand how individual patient preferences for the various treatment outcomes influence the optimal treatment decision for a given patient. METHODS: A Markov model was used to simulate treatment with total colectomy with an ileo pouch-anal anastomosis (TC/IPAA), cyclosporine (CSA), infliximab (INFLX), and infliximab followed by cyclosporine for treatment failures (INFLX-->CSA). Utility weights for treatment outcomes were elicited from 48 patients using both time trade-off and visual rating scale methods. Preference sets were applied to the model to identify the therapy that maximized quality-adjusted life years (QALYs) for each patient. Sensitivity analyses were performed to assess model robustness. RESULTS: Optimal treatment was highly variable among patients (INFLX-->CSA = 42%, 20/48; TC/IPAA = 37%, 18/48; CSA = 21%, 10/48; INFLX = 0%, 0/48). However, when average preference weights from our sample were applied to the model, medical treatments were superior to TC (CSA = .26 QALYs gained vs TC/IPAA; INFLX-->CSA = .25 QALYs gained vs TC/IPAA). CONCLUSIONS: Patient preferences have a clear impact on the optimal treatment for steroid-refractory ulcerative colitis. Although averaged preferences support the use of medical interventions, a third of individual patients may benefit most from proceeding directly to colectomy. Failure to fully assess individual preferences may result in suboptimal treatment for these patients.     

比较环孢菌素与英夫利息单抗治疗重症难治性溃疡性结肠炎疗效的荟萃分析

目的比较环孢菌素与英夫利息单抗治疗重症难治性溃疡性结肠炎后结肠切除率及并发症发生率。方法检索PubMed、EMBASE、Cochrane Library数据库中所有关于比较环孢菌素与英夫利息单抗治疗重症难治性溃疡性结肠炎的研究。应用比值比(OR)及其95%CI为疗效分析统计量。用Review Manager 5.1软件对符合纳入标准的研究通过固定效应模式或随机效应模式进行荟萃分析,比较使用环孢菌素和英夫利息单抗后的3个月、12个月的结肠切除率及并发症的发生率。结果共9篇文献纳入荟萃分析。其中,6篇为回顾性研究,2篇为前瞻性研究,1篇为多中心随机对照研究。对于3个月的结肠切除率,OR值为1.48(95%CI:0.61~3.62,P=0.39);对于12个月的结肠切除率,OR值为1.36(95%CI:0.59~3.12,P=0.47);对于并发症的发生率,OR值为0.88(95%CI:0.54~1.41,P=0.59)。结论英夫利息单抗和环孢菌素在治疗重症难治性溃疡性结肠炎后的结肠切除率和并发症的发生率差异均无统计学意义。     

Effect of infliximab in the treatment of refractory inflammatory bowel disease with complication]

BACKGROUND/AIMS: Many studies on infliximab have confirmed its efficacy in the remission induction and even maintenance in refractory and fistulizing Crohn's disease. We report the treatment efficacy of infliximab in Crohn's disease and ulcerative colitis refractory to steroid treatment and the complications of infliximab treatment. METHODS: We performed infliximab administration in 5 cases (3 Crohn's disease, 2 ulcerative colitis) refractory to systemic steroid treatment and 5 cases of Crohn's disease with fistula. Patients received an intravenous infusion of infliximab at 3-5 mg/kg body weight. RESULTS: In 3 cases of refractory Crohn's patients, clinical response and remission induction were obtained in 2 (67%) and 1 cases (33%). After infusion of infliximab, the occlusion of internal fistula could be found in all 2 cases. Two out of 3 cases of anal fistula were completely healed. In two cases of refractory ulcerative colitis, one case who showed clinical manifestation of toxic megacolon had improved and avoided the colectomy, but the other case did not respond to the infusion of infliximab and underwent colon resection. CONCLUSIONS: We found that administration of infliximab is an effective alternative for refractory and fistulizing Crohn's disease but further studies are necessary for refractory ulcerative colitis.     

Use of infliximab in the prevention and delay of colectomy in severe steroid dependant and refractory ulcerative colitis

AIM： To determine if infliximab can prevent or delay surgery in refractory ulcerative colitis （UC）. METHODS： UC patients who failed to have their disease controlled with conventional therapies and were to undergo colectomy if infliximab failed to induce a clinical improvement were reviewed. Patients were primarily treated with a single 5 mg/kg infliximab dose. The Colitis Activity Index （CAI） was used to determine response and remission. Data of 8 wk response and colectomy rates at 6 mo and 12 mo were collected. RESULTS： Fifteen patients were included, 7 with UC unresponsive or intolerant to Ⅳ hydrocortisone, and 8 with active disease despite oral steroids （all but one with therapeutic dosage and duration of immunomodulation）. All the Ⅳ hydrocortisone-resistant/intolerant patients had been on azathioprine/6-MP 〈 8 wk. At 8 wk, infliximab induced a response in 86.7% （13/15） with 40% in remission （6/15）. Within 6 mo of treatment 26.7% （4/15） had undergone colectomy and surgery was avoided in 46.6% （7/15） at 12 mo. The colectomy rate at 12 mo in those on immunomodulatory therapy 〈 8 wk at time of infliximab was 12.5% （1/8） compared with 100% （7/7） in patients who were on long-term maintenance immunomodulators （P 〈 0.02）. CONCLUSION： Infliximab prevented colectomy due to active disease in immunomodulatory-na？ve, refractory UC patients comparable to the use of Cyclosporine. In patients, however, on effective dosage and duration of immunomodulation at time of infliximab therapy colectomy was not avoided.