Predictive factors of clinical response in steroid-refractory ulcerative colitis treated with granulocyte-monocyte apheresis

AIM:To identify factors predicting the clinical response of ulcerative colitis patients to granulocyte-monocyte apheresis (GMA). METHODS:Sixty-nine ulcerative colitis patients (39 F,30 M) dependent upon/refractory to steroids were treated with GMA. Steroid dependency,clinical activity index (CAI),C reactive protein (CRP) level,erythrocyte sedimentation rate (ESR),values at baseline,use of immunosuppressant,duration of disease,and age and extent of disease were considered for statistical analysis as predicti...     

Azathioprine is essential following cyclosporine for patients with steroid-refractory ulcerative colitis

AIM: To evaluate long-term prognosis following cyclosporine treatment by examining the rate of surgery avoidance among cyclosporine responders.METHODS: We retrospectively reviewed clinical records for 29 patients diagnosed with severe steroid-refractory ulcerative colitis in our hospital from August 1997 to August 2008 and treated with cyclosporine by continuous intravenous infusion.All patients were treated with intravenous corticosteroids for more than 5 d prior to cyclosporine therapy.Administration was continued for up to 21 d under serum monitoring to maintain cyclosporine levels between 400 and 600 ng/mL.Clinical activity was assessed before and after cyclosporine therapy using the clinical activity index score,with a reduction of ≥ 5 considered to indicate a response.Among responders,we defined cases not requiring surgery for more than 5 years as exhibiting long-term efficacy of cyclosporine.Factors considered to be possibly predictive of long-term efficacy of cyclosporine were sex,age,disease duration,clinical activity index score,C-reactive protein level,hemoglobin level,disease extent,endoscopic findings,and clinical course.RESULTS: Cyclosporine was not discontinued due to side effects in any patient.Nineteen(65.5%) of 29 patients were considered responders.A statistically significant(P = 0.004) inverseas sociation wa s observed between an endoscopic finding of "mucosal bleeding" and responsive cases.Fifteen(9 males,6 females) of these 19 patients were followed for 5 years or more,of whom 9(60%) exhibited long-termefficacy of cyclosporine.Of the 10 non-responders,9(90%) underwent surgery within 6 mo of cyclosporine therapy.None of the following factors had a significant impact on the long-term efficacy of cyclosporine: sex,age,duration of disease,clinical activity index score,C-reactive protein level,hemoglobin level,extent of disease,endoscopic findings,or clinical course.In contrast,a significant association was observed for maintenance therapy with azathioprine after cyclosporine therapy(P = 0.0014).CONCLUSION: Maintenance therapy with azathioprine might improve the long-term efficacy of continuously infused cyclosporine for severe steroid-refractory ulcerative colitis patients.     

Oral microemulsion cyclosporine in the treatment of steroid-refractory attacks of ulcerative and indeterminate colitis.

BACKGROUND: To assess the efficacy of oral microemulsion cyclosporine (CyA Neoral) in the treatment of steroid-refractory attacks of ulcerative an indeterminate colitis. METHODS: In this non-randomized study on the use of oral microemulsion cyclosporine in steroid refractory ulcerative colitis, we used CyA Neoral in 10 patients suffering from ulcerative colitis and in 1 patient suffering from indeterminate colitis with a steroid-refractory attack. The initial dose was 7-7.5 mg kg-1 day-1 adjusted to maintain whole blood cyclosporine levels between 250 and 350 ng/mL, as measured by RIA using monoclonal antibodies. RESULTS: Nine patients presented a favourable response in a mean time of 3.6 days, that is, 81.8% of cases. One initial responder developed megacolon on the 11th day and another did not respond; surgical treatment was performed in both cases. The remaining nine patients, followed for a mean period of 14.6 months (2-36 months). Nine patients presented side effects, the most frequent being slight hand tremor with hypomagnesaemia, followed by hypertension, slight increase in creatinine and hirsutism. No one needed to withdraw from treatment, but the dose was lowered in three cases. CONCLUSIONS: Oral microemulsion cyclosporine is an effective drug in the initial management of patients suffering from a steroid-refractory attack of ulcerative and indeterminate colitis. Additional controlled studies with the new oral formulation are required to confirm these results.     

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.     

Predictive factors for the response of ulcerative colitis patients during the acute-phase treatment

Twenty-six consecutive admissions of 24 patients with severe ulcerative colitis (UC) hospitalized in our Department at some time between January 1983 and December 1988 were studied to identify factors useful in the prediction of response to medical treatment in the acute inflammatory phase of this disease. Results of laboratory tests (white blood cells, red blood cells, platelet count, hemoglobin, erythrocyte sedimentation rate, total protein, albumin, alpha 2-microglobulin, cholinesterase, total cholesterol, and triglycerides) and of endoscopic findings (extent of disease, progress of the lesions, sparing of the rectum, and presence of geographic ulcers, longitudinal ulcers, and polypoid mucosal tags) were analyzed for any relationship with the effect of medical treatment during the acute phase. The effect of treatment was evaluated in terms of days it took for a severe condition to improve to an intermediate one defined by Truelove and Witts' categories for UC severity. C-Reactive protein, nutritive condition (total protein, albumin, and cholinesterase), extent of the lesions, and existence of polypoid mucosal tags provide predictive factors useful in the management of UC during the acute phase.     

溃疡性结肠炎患者激素抵抗预测因素分析

目的回顾性分析激素抵抗和激素有效患者的临床资料,找出激素抵抗的预测因素,对临床用药起到一定的指导作用。方法检索我院1995年1月～2009年5月期间收治的210例溃疡性结肠炎(UC)患者的临床资料,对其一般资料、临床表现、激素的应用情况、实验室检查及内镜下表现进行系统分析。将其中应用激素的患者根据激素的治疗效果分为激素有效组、激素抵抗组和激素依赖组。对所收集的变量进行单因素和多因素Logistic回归分析。结果本研究中,激素抵抗UC患者占接受激素治疗患者总数的24.7%。在单因素分析中,性别(P=0.035)、全结肠受累(P=0.00)、白蛋白水平(P=0.04)以及根据Truelove和Witts分度为重度(P=0.00)四个因素与激素抵抗相关。在多因素分析中,只有男性(P=0.035)和低白蛋白水平(P=0.023)有显著性差异。结论经多因素Logistic回归分析,男性和白蛋白水平低下是激素抵抗的预测因素之一。研究UC激素抵抗发生的相关机制和预测方法,对于这些患者的治疗有着非常重要的意义。     

Infliximab versus cyclosporine as rescue therapy in acute severe steroid-refractory ulcerative colitis: a systematic review and meta-analysis

Purpose

Acute severe colitis affects 25 % of patients with ulcerative colitis (UC). Up to 30–40 % of these patients are resistant to intensive steroid therapy and therefore require rescue therapy to prevent emergent colectomy. Data comparing rescue therapy using infliximab and cyclosporine are limited and equivocal. This study evaluates the outcomes of UC patients receiving infliximab or cyclosporine as rescue therapy in acute severe steroid-refractory exacerbations.

Methods

Electronic databases (PubMed, EMBASE, and Cochrane database) were searched for studies directly comparing infliximab and cyclosporine in UC, and references of included studies were screened. Two independent reviewers identified relevant studies and extracted data. Meta-analyses were performed using the random effect model. Outcome measures included 3- and 12-month colectomy rates, adverse drug reactions, and postoperative complications.

Results

Six retrospective cohort studies describing 321 patients met the inclusion criteria. The meta-analysis did not show significant differences between infliximab and cyclosporine in the 3-month colectomy rate (odds ratio (OR)?=?0.86, 95 % confidence interval (CI)?=?0.31–2.41, p?=?0.775), in the 12-month colectomy rate (OR?=?0.60, 95 % CI?=?0.19–1.89, p?=?0.381), in adverse drug reactions (OR?=?0.76, 95 % CI?=?0.34–1.70, p?=?0.508), and in postoperative complications (OR?=?1.66, 95 % CI?=?0.26–10.50, p?=?0.591). Funnel plot revealed no publication bias.

Conclusions

Infliximab and cyclosporine are comparable when used as rescue therapy in acute severe steroid-refractory UC. Randomized trials are required to further evaluate these agents.

     

Intravenous cyclosporine in attacks of ulcerative colitis

The present study reports the results of intravenous cyclosporine in 32 patients with refractory and/or severe attacks of ulcerative colitis (UC). Twenty of 32 patients responded to intravenous cyclosporine; cyclosporine was clinically effective and improved colonic lesions. However, one colonic perforation and one postoperative death were observed in two patients with severe endoscopic colitis who had failed to reach clinical remission with high-dose corticosteroids and cyclosporine. Moreover, after a median follow-up of 190 days, only one-third of the patients avoided colectomy. No predictive factor of response to cyclosporine was identified. This study confirms that cyclosporine is effective in severe UC but suggests that its use could be associated with serious complications in patients with severe lesions who had failed to settle with corticosteroids and cyclosporine.     

Early colectomy in steroid-refractory acute severe ulcerative colitis improves operative outcome

Purpose

Up to a third of patients with acute severe ulcerative colitis (ASUC) fail to respond to intensive steroid therapy and eventually require a salvage colectomy. We have previously reported that the mortality of emergency colectomy can be decreased by offering it within the first week of intensive medical therapy. We implemented this policy and report the results of our experience.

Methods

The clinical records of all patients with ASUC who underwent emergency colectomy after failure of medical therapy between January 2005 and July 2015 were extracted from a prospectively maintained database. The data were analysed with regard to duration of intensive medical therapy, timing of surgery, in-hospital mortality and post-operative complications.

Results

Eighty-eight patients underwent emergency surgery for ASUC after failed medical therapy. Of these, 75 (85.2%) were operated within 7 days of initiation of intensive medical therapy [n = 51 (58%) were operated < 5 days]. One patient who was operated on day 8 following steroid therapy died postoperatively. The current post-operative mortality of 1.1% (1/88) was significantly lower than the mortality noted in the previously recorded retrospective case series [8/51 (15.6%); p = 0.001]. In addition, the incidence of overall (9/13 vs. 23/75; p = 0.012) and clinically significant (12/75 vs. 6/13; p = 0.022) complications was significantly higher in patients operated after 7 days as compared to those operated within 7 days.

Conclusion

The policy of early colectomy, within 7 days, in patients with ASUC who fail to respond to intensive steroid-based therapy improves perioperative outcomes with significantly low in-hospital mortality and morbidity.

     

Performance of tacrolimus in hospitalized patients with steroid-refractory acute severe ulcerative colitis

BACKGROUND Acute severe ulcerative colitis unresponsive to systemic steroid treatment is a lifethreatening medical condition requiring hospitalization and often colectomy.Despite the increasing choice of medical therapy options for ulcerative colitis, the condition remains a great challenge in the field of inflammatory bowel diseases(IBD). The performance of the calcineurin inhibitor tacrolimus in this clinical setting is insufficiently elucidated.AIM To evaluate the short and long-term outcomes of tacrolimus therapy in adult inpatients with steroid-refractory acute severe ulcerative colitis.METHODS We conducted a retrospective monocentric study enrolling 22 patients at a tertiary care center for the treatment of IBD. All patients who were admitted to one of the wards of the Department of Gastroenterology and Hepatology of the Heidelberg University Hospital with acute severe ulcerative colitis between 2007 and 2018, and who received oral or intravenous tacrolimus for steroid-refractory disease were included. Baseline characteristics and data on the disease courses were retrieved from entirely computerized patient charts. The primary study endpoint was clinical response to tacrolimus therapy, resulting in discharge from the hospital. Secondary study endpoints were colectomy rate and time to colectomy, achievement of clinical remission under tacrolimus therapy, and the occurrence of side effects.RESULTSIn the majority of the 22 included patients(68.2%), tacrolimus therapy was initiated intravenously and subsequently converted to oral administration. The treatment duration was 128 ± 28.5 d(mean ± SEM), and the patients were followed up for 705 ± 110 d after treatment initiation. Among all patients, 86.4%were discharged from the hospital under continued oral tacrolimus therapy. In36.4% of the patients, the administration of tacrolimus resulted in clinical remission at some point during the treatment. Thirty-two percent of the patients underwent colectomy between 5 and 194 d after the initiation of tacrolimus treatment(mean: 97.4 ± 20.8 d). Colectomy-free survival rates at 1, 3, 6 and 12 mo after the initiation of tacrolimus therapy were 90.9%, 86.4%, 77.3% and 68.2%,respectively. The safety profile of tacrolimus was overall favorable. Only two patients discontinued the treatment due to side effects.CONCLUSION The short-term outcome of tacrolimus in steroid-refractory acute severe ulcerative colitis was beneficial, and side effects were rare. In all, tacrolimus therapy appears to be a viable option for short-term treatment of steroidrefractory acute severe ulcerative colitis besides ciclosporin and anti-tumor necrosis factor α treatment.     

Infliximab in patients with severe steroid-refractory ulcerative colitis: Indian experience

Introduction

The role of infliximab in the treatment of acute severe ulcerative colitis is established. However, all the data available in the literature are from western countries. This is the first report on the use of infliximab in patients with severe steroid-refractory ulcerative colitis from India.

Methods

Retrospective analysis of 28 patients who had received infliximab therapy for induction of remission, with three doses of 5 mg/kg at 0, 2, and 6 weeks, was performed.

Results

Twenty-four (85.6 %) patients had shown a clinical response by week 8 and, hence, avoided urgent colectomy. In 2 years of follow up, 9/16 (56 %) patients had not required colectomy.

Conclusion

Infliximab averted colectomy in a proportion of patients with severe steroid-refractory ulcerative colitis.     

Predictive factors of efficacy of leukocytapheresis for steroid-resistant ulcerative colitis patients

BACKGROUND: The effectiveness of leukocytapheresis against ulcerative colitis has been reported. However, the efficacy of this therapy for steroid-resistant ulcerative colitis patients has hardly been examined. AIMS: The aims of this study are to evaluate the efficacy of leukocytapheresis for steroid-resistant ulcerative colitis patients and to identify clinical factors that predict the efficacy of this therapy for these patients. METHODS: Clinical factors of 71 steroid-resistant ulcerative colitis patients who underwent leukocytapheresis analysed. RESULTS: Of those analysed, 53 (75%) patients showed an initial response to leukocytapheresis. Among cases with initial response, however, only 19 (27%) patients maintained remission for more than 6 months. Steroid-dependent course (Odds ratio =5.53, 95% confidence interval; 1.24-24.73) and a high C-reactive protein degree (Odds ratio=1.6, confidence interval; 1.09-2.35) were predictors of initial response to leukocytapheresis. Rapid response, which means remission induction within three leukocytapheresis sessions, was the only predictor of maintenance of remission for more than 6 months after successful leukocytapheresis therapy (odds ratio=8.01, confidence interval; 1.08-59.37). CONCLUSIONS: Leukocytapheresis was effective for steroid-resistant ulcerative colitis patients. However, relapse was frequently observed within short periods after the initial response to this therapy. Patients without a rapid response should be treated with alternative or additional therapies.     

Predictors of a response to cyclosporine or leukocyte removal therapy in patients with refractory ulcerative colitis

Introduction: Despite decades of clinical experience in optimizing the induction and maintenance of remission in patients with ulcerative colitis (UC), some patients remain refractory to conventional medical treatment while, in others, the effectiveness of drugs is limited by side‐effects. We investigated factors predictive of the efficacy of cyclosporine and leukocyte removal therapy in patients with intractable UC. Methods: Forty‐five patients with moderate to severe UC who were refractory to corticosteroid therapy were enrolled. Twenty‐six patients were treated with cyclosporine and 19 by leukocyte removal therapy. Disease activity index (DAI) score assessment, and colonoscopic and histological examinations were done before and at 10, 20 and 40 days after the initiation of treatment. A clinical response to treatment was defined as a decrease in DAI score of 3 points or more at 40 days. Results: Responder ratio did not significantly differ between the cyclosporine (65.6%) and leukocyte removal therapy (63.2%) groups. Factors predictive of a response to cyclosporine therapy were fever (≥ 38.0°C), anemia and large mucosal ulceration. In contrast, mucosal bleeding and poor extensibility of the intestinal lumen were predictive of a poor response to cyclosporine. No significant differences in any clinical or endoscopic parameter predictive of a response to leukocyte removal therapy were identified. Conclusions: Intravenous cyclosporine may be effective in patients who have severe steroid‐refractory UC, and leukocyte removal therapy may be useful in patients with moderate active UC predicted to be refractive to cyclosporine.