Treatment Of Severe Ulcerative Colitis Research Articles

Outcomes of Partial Versus Total Colectomy in Ulcerative Colitis: A Propensity Score-Matched Analysis

IntroductionTotal abdominal colectomy (TAC) with ileostomy is the standard treatment for severe ulcerative colitis (UC). Partial colectomy (PC) with colostomy may present a less morbid treatment option. MethodsThe 2012-19 ACS-NSQIP database was queried to assess 30-day outcomes among patients undergoing TAC versus PC for UC, utilizing propensity score matching (PSM) techniques to account for differences in disease severity, patient selection, and presentation acuity. ResultsBefore matching (n = 9888), patients undergoing PC were older, had more comorbidities, and experienced higher complication and 30-day mortality rates (P < 0.001). After matching (n = 1846), patients undergoing TAC experienced higher 30-day overall complications (41.9% versus 36.5%, P = 0.017) and serious complications (37.2% versus 31.5%, P = 0.011). Sensitivity analyses of older patients and those undergoing nonemergency surgery demonstrated higher overall rates of complications for patients receiving TAC. However, among patients undergoing emergency surgery only, no differences in complications were seen between the two surgical approaches. ConclusionsPC with colostomy in the setting of ulcerative colitis has similar 30-day outcomes to TAC with ileostomy. PC may be an acceptable surgical alternative to TAC in select patients. Studies investigating longer-term outcomes are necessary to further investigate this option.

Effects of Dextran Sulfate Sodium-Induced Ulcerative Colitis on the Disposition of Tofacitinib in Rats.

Tofacitinib, a Janus kinase 1 and 3 inhibitor, is mainly metabolized by CYP3A1/2 and CYP2C11 in the liver. The drug has been approved for the chronic treatment of severe ulcerative colitis, a chronic inflammatory bowel disease. This study investigated the pharmacokinetics of tofacitinib in rats with dextran sulfate sodium (DSS)-induced ulcerative colitis. After 1-min of intravenous infusion of tofacitinib (10 mg/kg), the area under the plasma concentration-time curves from time zero to time infinity (AUC) of tofacitinib significantly increased by 92.3%. The time-averaged total body clearance decreased significantly by 47.7% in DSS rats compared with control rats. After the oral administration of tofacitinib (20 mg/kg), the AUC increased by 85.5% in DSS rats. These results could be due to decreased intrinsic clearance of the drug caused by the reduction of CYP3A1/2 and CYP2C11 in the liver and intestine of DSS rats. In conclusion, ulcerative colitis inhibited CYP3A1/2 and CYP2C11 in the liver and intestines of DSS rats and slowed the metabolism of tofacitinib, resulting in increased plasma concentrations of tofacitinib in DSS rats.

2075 Tandem Therapy Using Cyclosporine and Tofacitinib for the Treatment of Severe Ulcerative Colitis

INTRODUCTION: Although there are evolving options for the treatment of ulcerative colitis (UC), the timing and sequencing of newer treatments has not been sufficiently studied. Tofacitinib (tofa) is a non-selective Janus kinase inhibitor that is now available for patients with moderately to severely active UC, but its use in combination with other therapies has been limited due to trial design, labeling and evolving experience in these patients. We present a patient with medically refractory severe UC who was successfully treated with cyclosporine and then maintained with tofa. CASE DESCRIPTION/METHODS: A 24-year-old man with a history of primary sclerosing cholangitis (PSC) and overlap auto-immune hepatitis (AIH) was diagnosed with ulcerative pancolitis at the age of 20. He was maintained in clinical remission for two years with mesalamine. A subsequent clinical relapse required steroid therapy, then vedolizumab loading and q8w maintenance, but due to incomplete response, he was escalated to monthly infusions and after clarification of his overlapping liver disease, azathioprine was added. Despite these treatments, he was symptomatic, steroid-dependent, and had persistent evidence of endoscopic inflammation, CRP 29 mg/L and albumin 3.3 g/dL. Infliximab (IFX) 10 mg/kg loading and q8w dosing was initiated, but he was still steroid-dependent despite IFX trough 11 μg/mL. IFX was increased to 10 mg/kg q4w. Due to lack of response, he was admitted for IV cyclosporine (CsA). CsA at 3 mg/kg continuous infusion was initiated and titrated to a target serum level of 300-400 ng/ml. By day 6 he was in near clinical remission and discharged on oral CsA 200 mg BID. He was then transitioned from prednisone to ileal-release budesonide (for his liver disease). After two months of sustained clinical remission we stopped the CsA for 48 hrs and then initiated tofa at 10 mg PO twice a day. At 17-month follow-up he remains in clinical remission receiving tofa 10 mg BID and budesonide 6 mg daily, and has a normal CRP and normal liver enzymes. DISCUSSION: This is a patient with medically resistant UC, PSC and AIH successfully induced into deep remission using CsA and maintained with tofa (and budesonide for his liver disease, azathioprine should not be used with tofa). The half-life of cyclosporine (8.5 hrs) allowed for short washout period prior to initiation of tofa, and therefore prevented the risk of overlapping immune suppression and toxicity. This is the first report of such a combination therapy approach.

Infliximab in therapy of inflammatory bowels diseases

Introduction. Infliximab is a monoclonal antibody that acts against tumor necrosis factor TNF-α. The drug is used in the treatment of autoimmune diseases. Aim. This article reviewed the efficacy and safety of infliximab for the treatment in severe ulcerative colitis. This review included studies that evaluated the clinical use of infliximab. Material and methods. This meta-analysis was performed according to systematic literature search of three major bibliographic databases (Scopus, PubMed, and Cochran). Results. Infliximab has been approved by the US Food and Drug Administration (FDA) as a medicine to treat Leśniowski and Crohn’s disease, ulcerative colitis, psoriasis, psoriatic arthritis, ankylosing spondylitis, and rheumatoid arthritis. However, further trials are required to compare other parameters of efficacy such as the clinical response with infliximab. Conclusion. In patients suffering from Crohn’s disease or ulcerative colitis under infliximab maintenance therapy, sustained good trough levels are associated with: better response and remission rates, more mucosal healing and less loss of response.

Tacrolimus Exerts Only a Transient Effectiveness in Refractory Pediatric Crohn Disease: A Case Series.

Tacrolimus is an immunosuppressive agent that has been proposed in the treatment of severe ulcerative colitis. The present study examined the effectiveness and safety of tacrolimus in treating refractory Crohn disease (CD) colitis in children. All children treated by oral tacrolimus for CD colitis at a tertiary pediatric center were included in the study. All patients were refractory to steroids and infliximab. Clinical response (decreased pediatric CD activity index [PCDAI] >15 and PCDAI <30) and remission (PCDAI <10) were monitored at 2, 4, 6, 12, and 24 months after induction. Tacrolimus blood levels and adverse effects were also noted. Among 220 patients with CD, 8 children (including 3 girls, median age 14 [9.5-18] years) were registered with a median PCDAI of 58.7 (32.5-65) before tacrolimus initiation. In patients treated with tacrolimus, the overall clinical response rates were 6/8, 3/8, 2/8, 2/8, and 1/8 with a remission rate of 4/8, 0/8, 0/8, 2/8, and 0/8 at 2, 4, 6, 12, and 24 months, respectively. At 2 months, the PCDAI scores were lower than those at induction (median 11.2; P = 0.004) with the mean whole plasma level of tacrolimus being 8.75 ng/mL (5.9-10 ng/mL). Adverse events occurred in 6 of 8 patients, including renal dysfunction, insulin-dependent diabetes, paresthesia, and tremor. Tacrolimus interruption was required in 2 cases. Tacrolimus could be considered to transiently treat refractory CD colitis. Tacrolimus could be used as a "bridge" toward another medical option in pediatric CD, although its adverse events are frequent.

EFFICACY OF TACROLIMUS FOR INDUCTION OF REMISSION IN PATIENTS WITH MODERATE-TO-SEVERE ULCERATIVE COLITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS.

There is evidence that shows that calcineurin inhibitors may be useful for the treatment of severe ulcerative colitis. However, evidence regarding the efficacy of tacrolimus for remission induction in this setting is scarce. To develop a systematic review on the existing evidence regarding the clinical efficacy of tacrolimus for the induction of remission in patients with moderate-to-severe ulcerative colitis. A literature search was undertaken from 1966 to August 2016 using MEDLINE, Embase, LILACS and the Cochrane Library. The following MeSH terms were used: "Inflammatory Bowel Diseases" or "Ulcerative Colitis" and "Calcineurin Inhibitors" or "Tacrolimus" or "FK506". Studies performed in adult ulcerative colitis patients that evaluated the clinical efficacy of tacrolimus for the induction of remission were considered for revision. A meta-analysis was performed with those included studies that were also placebo-controlled and randomized. Clinical response as well as clinical remission and mucosal healing were evaluated. Overall, 755 references were identified, from which 22 studies were finally included. Only two of them were randomized, placebo-controlled trials. A total of 172 patients were evaluated. A significantly lower risk of failure in clinical response was found for tacrolimus versus placebo [RR 0.58 (0.45-0.73)]; moreover, a lower risk of failure in the induction of remission was also found versus placebo [RR 0.91 (0.82-1)]. Tacrolimus seems to be a valid therapeutic alternative for the induction of remission in patients with moderate-to-severe ulcerative colitis.

Long-Term Outcomes After Cyclosporine vs. Infliximab for Acute Severe UC

Cyclosporine and infliximab have comparable short-term efficacy for the treatment of steroid-refractory acute severe ulcerative colitis (UC). Now,

Tu1307 Using Serum Infliximab Drug and TNF Cytokine Concentration to Predict Clinical Outcome After High-Dose Infliximab in the Treatment of Severe Ulcerative Colitis: A Pilot Study

Background: Over 50% of hospitalized patients with severe ulcerative colitis (UC) require emergent colectomy despite receiving standard dose infliximab (IFX) at 5 mg/kg. Proposed reasons for failure include rapid clearance of IFX from the serum due to fecal loss of IFX, prompting some centers to empirically prescribe high dose IFX at 10 mg/kg. While this strategy is reasonable, the acute pharmacokinetics of this strategy is unknown and reasons for failure using this strategy are poorly described. Methods: In a prospective pilot study, 11 adult hospitalized patients (7 men, 4 women) with severe UC confirmed by sigmoidoscopy (UCDAI > 6, Mayo endoscopic subscore > 2) received 10 mg/kg of IFX within 3-5 days of initiating IV steroids. Measurement of IFX drug concentration and TNF-alpha levels occurred at baseline and at 24, 48, and 72 hours, and at 1 and 2 weeks after the initial infusion. MadCam (mucosal vascular addressin cell adhesion molecule) cytokine concentration served as a control. The association between these markers and surgery was analyzed. Results: Three patients required colectomy within the 8 week study period (27%). Median IFX drug concentration was comparable in the colectomy and no colectomy groups at all time points. While drug concentration at any time point did not discriminate between the two groups, the response of TNF-alpha cytokine concentration to IFX did. Both groups had similar TNF concentration at baseline, however the colectomy group had higher TNF concentration 24 hours after TNF inhibitor therapy (p=0.03). Control MadCam concentration was similar and unchanged in both groups receiving TNF inhibitor therapy. Conclusion: Our study suggests lower IFX drug concentration is not an important mechanism for TNF-inhibitor failure in severe UC patients receiving high dose IFX, however response to TNF inhibition as measured by TNF concentration at 24 hours is. Larger cohorts are needed to define the role of using cytokine response to biologic therapy to help elucidate the mechanism and predict biologic failure in this high risk group.

Tratamiento del brote grave de colitis ulcerosa

The treatment of severe ulcerative colitis remains a challenge for gastroenterologists. A not inconsiderable number of patients will experience severe flares throughout their lives and will require hospitalization. Mortality in severe ulcerative colitis is still high and consequently treatment must be aggressive, avoiding delays in rescue therapies or even surgery.The aim of this review was to describe the medical treatment of severe ulcerative colitis, highlighting recent therapeutic advances.

Early predictors of responses and clinical outcomes of corticosteroid treatment for severe ulcerative colitis

Background. Patients with severe ulcerative colitis (SUC) have a high risk of requiring colectomy or resorting to a second-line treatment. However, neither clinical outcomes nor factors predictive of poor response have been clearly established in the treatment of SUC. Objective. To assess prospectively the effects and predictors of corticosteroids (CS) use in clinical outcomes of SUC during 1 year of follow-up. Material and methods. Consecutive inpatients with SUC, who had been treated with intravenous CS, were enrolled. Patients were monitored by clinical, laboratory, and endoscopic examinations, and the data were recorded for 1 year. Univariate and multivariate analyses were performed at 1 week. Results. There were 22.6% (14/62) nonresponders at 7 days. Several predictors were associated with nonresponse to CS. These included Mayo Score at baseline (p = 0.007), partial Mayo Score, number of bowel movements, blood presence in stool, abdominal pain, and levels of C-reactive protein (CRP), hemoglobin (Hgb), platelet count (PLT), and erythrocyte sedimentation rate (ESR) on day 3 (p < 0.05). Multiple logistic regression analysis identified the Partial Mayo Score at day 3 as an independent predictor of outcome (p = 0.012). A total of 12 patients underwent colectomy within 1 year. The short-term response rates to intravenous cyclosporin (CsA) and infliximab (IFX) in SUC were 71.4% (5/7) and 77.8% (7/9), respectively. Conclusions. Many patients with SUC eventually became refractory to or dependent on CS. The Mayo score and laboratory characteristics were factors useful in predicting short-term outcome of CS treatment. Secondary medical therapy can help avoid emergency surgery.

P-006 YI Treatment of Severe Ulcerative Colitis with Cyclosporine Less than 30 Days Post Acute Myocardial Infarction and Heart Failure

When intravenous (IV) steroids fail, severe ulcerative colitis (UC) is treated with cyclosporine, infliximab, or surgery. Currently, advanced heart failure is an absolute contraindication for tumor necrosis factor-alpha antagonists because of the risk of increased mortality and worsening heart failure (1,2). Cyclosporine may decrease myocardial reperfusion injury and improve left ventricular remodeling (3–8). We present a case of a patient with acute myocardial infarction (MI) and heart failure whose severe colitis was treated successfully with cyclosporine. A literature search was performed using multiple search engines (PubMed, EMBASE, CINAHL) for cases with ulcerative colitis and myocardial infarction as well as ulcerative colitis, myocardial infarction, and heart failure. A 58 year-old Haitian male with a past medical history of coronary artery disease with stents in 2001 and 2011 and history of UC, maintained on topical therapy for left-sided colitis, had a non-ST elevated myocardial infarction (NSTEMI) requiring a drug-eluting stent. Shortly after, he noticed rectal bleeding and self stopped both aspirin and clopidogrel. Two weeks later, he had a STEMI with 100% occlusion and stent re-stenosis; angioplasty and thrombectomy were performed emergently. Post-procedure echocardiogram showed ejection fraction of 30% and severely reduced left ventricular contractility. He continued to have bloody diarrhea and was found to have elevated inflammatory markers (erythrocyte sediment rate (ESR) 71, C-reactive protein (CRP) 129.4). The patient failed a trial of 5-aminosalicylates. A flexible sigmoidoscopy was consistent with severe UC. He was started on IV steroids, metronidazole, and hydrocortisone foam; 1 week later, symptoms persisted and his hemoglobin dropped to 6.2. A computed tomography scan showed pancolitis. Additionally, there was a concern for sepsis as his white blood cell count (WBC) dropped below 1,000 necessitating filgrastim. Due to his heart failure, infliximab was not an option. The mortality risk associated with colectomy was assessed to be >50% given his recent MI. He was therefore started on IV cyclosporine 2 mg/kg for 7 days; a lower dose of cyclosporine was used because of the patient’s low total cholesterol (102) and atorvastatin was held. Within 1 week, bowel movements were reduced to 3 per day, with less cramping, urgency, and tenesmus; inflammatory markers also improved (ESR 29, CRP 3.5). He was discharged on oral cyclosporine with a bridge to azathioprine. He is now 3 months post treatment and doing well. Repeat echocardiogram showed stable heart function and his WBC rose to normal and remained stable. Previous cases of UC and MI (9–14, Table 1) illustrate the various presentations, therapeutic options, and outcomes of similar patients. The only other case found in the literature of UC flare with STEMI and heart failure that was treated with cyclosporine required an emergent colectomy 2 weeks later (10). Options for treating severe UC in patients who are acutely post MI and with heart failure are limited. In this case, cyclosporine appeared to be a safer option than tumor necrosis factor-alpha antagonists.

Randomized Controlled Trials in Steroid Dependent and in Severe Colitis

Intravenous steroids are considered the mainstay of treatment in patients with severe ulcerative colitis. Several randomized controlled trials have been designed to evaluate drugs that, as an adjunct to intravenous steroids, could obtain a clinical response and avoid colectomy in patients who do not respond to corticosteroids. For steroid refractory patients, cyclosporine and infliximab seem to be an effective alternative to colectomy in the short term, but more data are needed to evaluate if they can prevent colectomy also in the long term. Although there is no evidence from the published trials that antibiotics as adjunctive therapy may have an additional benefit, therapeutic protocols for severe ulcerative colitis generally include antibiotics for patients with signs of toxicity, or with worsening of symptoms despite the medical treatment. No additional benefit over steroids has been shown from bowel rest. Moreover, as bowel rest deprives the colonic enterocytes of the short-chain fatty acids vital to their metabolism and repair, it may even be harmful. Conflicting results have been published on heparin as primary treatment of severe ulcerative colitis; at the present time there is no evidence supporting its use. Although "steroid-free" clinical remission is, at this time, the most important end point of clinical studies in inflammatory bowel disease, only few data are available in steroid dependent colitis patients. Azathioprine seems to be effective in inducing steroid-free remission.

Predictive factors of response to intravenous ciclosporin in severe ulcerative colitis: the development of a novel prediction formula

When treating patients with severe ulcerative colitis (UC), accurate prediction of drug efficacy contributes to early clinical decision-making. To identify predictive factors and to develop a reliable prediction formula and a decision tree of response to intravenous ciclosporin treatment for severe UC. Patients included in this study were those diagnosed with refractory severe UC who had undergone ciclosporin treatment between December 2004 and March 2011 at a tertiary referral centre in Japan. Demographic and clinical parameters from all patients were analysed by multivariate statistics. Fifty-two patients were included in this study (36.5% men with an average age of ciclosporin initiation of 40.2±15.6years). Thirty-four patients (65.4%) were responders to the treatment with ciclosporin and avoided colectomy, 18 patients (34.6%) were nonresponders and underwent colectomy. Stepwise multiple logistic regression analysis identified four independent predictive factors of response to intravenous ciclosporin: age at hospitalisation (AGE), platelet count (×10(4) /μL) on the first day (PLA), Lichtiger score on the third day (LIC) and total protein (g/dL) on the third day minus total protein on the first day (ΔTP). The calculation formula (8.5 - 0.16 × AGE + 0.21 × PLA - 0.61 ×LIC+2.3×ΔTP<0) predicted colectomy with an accuracy of 88.5% and the decision tree predicted colectomy with an accuracy of 90.4%. The novel calculation formula and the decision tree effectively predict the clinical outcome of ciclosporin treatment for severe ulcerative colitis as early as on day 3 after starting ciclosporin treatment.

Rapid endoscopic improvement is important for 1-year avoidance of colectomy but not for the long-term prognosis in cyclosporine A treatment for ulcerative colitis

Intravenous (IV) cyclosporine A (CSA) is one of the treatments of choice for patients with steroid-refractory severe ulcerative colitis (UC). In this study, we evaluated the overall experience with CSA treatment in UC patients, from their initial response to long-term prognosis. The medical records of 72 patients admitted to our hospital with a severe UC flare-up and treated with IV CSA between November 1996 and October 2008 were reviewed retrospectively. The initial response to CSA was assessed using a clinical activity index, and colectomy was assigned as the endpoint for the long-term prognosis. Overall, 53 of 72 (73.6%) patients responded initially to CSA. We could not determine any specific parameters that predicted an initial response. A life-table analysis for all patients revealed that 54.4% of patients required a colectomy within 11years. The long-term risk of surgery was associated with a shorter disease duration, history of adverse reactions against medications and lack of immunomodulator use. In addition, endoscopic improvement at day 14 was associated with colectomy at 1year, but not with the long-term prognosis. Although CSA can exert high initial efficacy for severe attacks of UC, >50% of patients who relapse require a colectomy. Specifically, mucosal healing evaluated by endoscopy was associated with the 1-year colectomy rate. In contrast, a history of adverse drug reactions was correlated with the long-term colectomy rate. Therefore, we propose that treatment of severe UC with CSA requires consideration of both initial remission and long-term maintenance as management goals.

Analysis of surgical treatment for severe ulcerative colitis

To evaluate the role of different procedures in the treatment of severe ulcerative colitis (UC) requiring colectomy. A total of 29 UC inpatients who underwent colectomy at the West China Hospital between January 1996 and December 2008 were included in this study. Except two cases who underwent partial colectomy, patients were divided into total colectomy group (TC group, n=7) and total proctocolectomy group (TPC group, n=20), meanwhile divided into ileal pouch-anal anastomosis (IPAA, n=8) group, straight end-to-end anastomosis (ileoanal or ileorectal and ileostomy) group (n=14)and ileostomy group (n=5). Quality of life (QOL) was assessed using the Cleveland Global Quality of Life (CGQL) instrument. The complication rate was 60.0% in TPC group and 57.1% in TC group (P>0.05). The recurrence rate was 15.0% in TPC group and 57.1% in TC group (P<0.05). The complication rate was 6/8 in IPAA group and 50.0% (7/14) in straight end-to-end anastomosis group (P>0.05). The frequency of daily bowel movements in IPAA group was significantly lower than that in straight end-to-end anastomosis group at 1 year after the surgery (5.6+/-1.7 versus 9.1+/-2.9, P<0.05). QOL was significantly improved postoperatively for all the patients(P<0.01). Patients who underwent IPAA had a better QOL than those of straight end-to-end anastomosis group (P>0.05). TPC-IPAA is the ideal procedure of severe UC with acceptable complication rate, satisfactory quality of life and functional outcome.

Proliferative T-Cell Responses in Steroid-Responsive and Steroid-Refractory Puerto Ricans with Ulcerative Colitis

Purpose: Ulcerative Colitis (UC) is an inflammatory process of unknown etiology. Glucocorticoids are a mainstay in anti-inflammatory treatment of UC. It has been suggested that steroid-refractory ulcerative colitis can be secondary to resistance of proliferating T cells to steroid inhibition. In-vitro testing of lymphocytes from patients with UC may shed light on the issue and could serve to classify patients before treatment. It is our purpose to investigate the presence of steroid resistant cells and its association with refractory disease in Puerto Ricans with Ulcerative Colitis. Methods: Adult Puerto Ricans with UC and controls were recruited at the IBD outpatient clinic. The population was divided in three groups: steroid responsive, steroid refractory and controls. Blood was drawn after consent, and the effects of steroids (prednisolone) on the antiproliferative effect on phytohaemagglutininstimulated peripheral T lymphocytes was assessed. An index of inhibition of proliferation (I max) was calculated. Inhibition of growth is defined as I max > 60%. Results: Thirty individuals were identified, eighteen completed the study. Five patients were in the groups of steroid responsive and steroid refractory each and eight individuals were controls. Unexpectedly, steroid responsive patients did not show inhibition of proliferation (mean 27%, median 25%, range 0-58%). As predicted, T lymphocytes of steroid refractory patients were not inhibited by steroids (mean 19%, median 13%, range 0-43%). Controls showed mixed results. Median values were not different between the 3 groups. Conclusion: There was a statistically significant difference between patient groups in terms of expected inhibition of proliferation (p= .01). In vitro T lymphocyte steroid sensitivity (I max) may be more important than disease severity in determining the response to steroid treatment in severe UC.

Role of endoscopic ultrasonography in predicting the response to cyclosporin A in ulcerative colitis refractory to steroids

Although cyclosporin A has been reported to be effective in the treatment of severe ulcerative colitis, factors predicting its therapeutic efficacy remain unclear. Technical progress in endoscopic ultrasonography has improved visualisation of the structure of the colon wall. Here, to assess the value of endoscopic ultrasonography in predicting the response to cyclosporin A treatment, we evaluated the therapeutic effect of cyclosporin A by determining the pre- and post-cyclosporin A thickness of the mucosal layer in the rectum using endoscopic ultrasonography with an ultrasonic catheter probe. Fifteen ulcerative colitis patients who did not respond to high-doses of corticosteroids were treated with cyclosporin A by continuous intravenous infusion at 4mg/kg/day for 20 days. Before and 20 days after cyclosporin A therapy, clinical disease activity was assessed using clinical activity index scores. Colonoscopy and endoscopic ultrasonography were undertaken before and 20 days after cyclosporin A therapy. Following treatment with cyclosporin A, nine patients showed a decrease in clinical activity index score by six points or more and were defined as responders, while the other six were defined as non-responders. Endoscopic ultrasonography measurement using an ultrasonic catheter probe showed that thickness of the rectal mucosal layer before cyclosporin A was significantly greater in responders than in non-responders (p<0.05). Further, thickness after cyclosporin A was statistically decreased (p<0.01) in the responders but not in the non-responders. The ultrasonic catheter probe may represent a useful means of predicting and evaluating the efficacy of cyclosporin A treatment in severely ill ulcerative colitis patients.

Predictive factors of poor response to intravenous cyclosporine in steroid-refractory ulcerative colitis

The treatment of severe ulcerative colitis (UC) flares includes measures such as hospitalization and intravenous steroids. Despite this, a quarter of patients are refractory to treatment. Given the availability of new therapeutic strategies in patients with steroid-refractory UC (cyclosporine, infliximab, apheresis, surgery) it is necessary to predict which treatment will be most effective for each patient. To determine which clinical or biological factors discriminate the lack of response to cyclosporine in steroid-refractory UC. Forty one flares of steroid-refractory UC in 35 patients treated with intravenous cyclosporine have been included. The response to cyclosporine was assessed at day 10 of treatment by using the modified Truelove and Witts disease activity score. Variables with prognostic significance were determined by a univariate analysis comparing groups with complete response and no-response, and an analysis of multiple linear regression. Complete response was obtained in 41 flares (48%), partial response in 22%, and lack of response in 29%. The univariate analysis showed a significant difference in four predictive factors: higher age (p = 0.008), thrombocytosis (p = 0.01), disease extent (pancolitis vs. left-sided disease (p = 0.04)), and having received cyclosporine previously (p = 0.01). A multiple linear regression analysis confirmed the significance of higher age, thrombocytosis, and having received cyclosporine previously as predictive factors of poor response. Higher age, thrombocytosis and previous use of cyclosporine predispose to poor response to intravenous cyclosporine in severe flares of steroid-refractory UC.

Current treatment for severe ulcerative colitis

Current treatment for severe ulcerative colitis

Is there a role for infliximab in the treatment of severe ulcerative colitis?

Is there a role for infliximab in the treatment of severe ulcerative colitis?