Steroid-resistant Ulcerative Colitis Research Articles

Infliximab versus ciclosporin in steroid resistant acute severe ulcerative colitis: a model-based cost-utility analysis of data from CONSTRUCT pragmatic trial

BackgroundThere is limited evidence in the literature on the long-term effectiveness and cost-effectiveness of treatments for Acute Severe Ulcerative Colitis (ASUC). The study aimed to perform decision analytic model-based long-term cost-utility analysis (CUA) of infliximab versus ciclosporin for steroid-resistant ASUC investigated in CONSTRUCT pragmatic trial.MethodsA decision tree (DT) model was developed using two-year health effect, resource use and costs data from CONSTRUCT trial to estimate relative cost-effectiveness of two competing drugs from the United Kingdom (UK) National Health Services (NHS) perspective. Using short-term trial data, a Markov model (MM) was then developed and evaluated over further 18 years. Both DT and MM were combined to investigate cost-effectiveness of infliximab versus ciclosporin for ASUC patients over 20-year time horizon, with a rigorous multiple deterministic and probabilistic sensitivity analyses to address uncertainty in results.ResultsThe decision tree mirrored trial-based results. Beyond 2-year trial follow-up, Markov model predicted a decrease in colectomy rate, but it remained slightly higher for ciclosporin. NHS costs and quality adjusted life years (QALYs) over base-case 20 year time horizon were £26,793 and 9.816 for ciclosporin and £34,185 and 9.106 for infliximab, suggesting ciclosporin dominates infliximab. Ciclosporin had 95% probability of being cost-effective at a willingness-to-pay (WTP) threshold value up to £20,000.ConclusionUsing data from a pragmatic RCT, the cost-effectiveness models produced incremental net health benefit in favour of ciclosporin relative to infliximab. Results from long-term modelling indicated that ciclosporin remains dominant compared with infliximab for the treatment of NHS ASUC patients, however, these need to be interpreted cautiously.Trial registrationCONSTRUCT Trial registration number ISRCTN22663589; EudraCT number: 2008-001968-36 (Date 27/08/2008).

Patient preferences and current practice for adults with steroid-resistant ulcerative colitis: POPSTER mixed-methods study.

Corticosteroids are a mainstay of the treatment of moderately severe relapses of ulcerative colitis, yet almost 50% of patients do not respond fully to these and risk prolonged steroid use and side effects. There is a lack of clarity about the definitions of steroid resistance, the optimum choice of treatment, and patient and health-care professional treatment preferences. The overall aim of this research was to understand how steroid-resistant ulcerative colitis is managed in adult secondary care and how current practice compares with patient and health-care professional preferences. A mixed-methods study, including an online survey, qualitative interviews and discrete choice experiments. NHS inflammatory bowel disease services in the UK. Adults with ulcerative colitis and health-care professionals treating inflammatory bowel disease. We carried out a survey of health-care professionals (n = 168), qualitative interviews with health-care professionals (n = 20) and patients (n = 33), discrete choice experiments with health-care professionals (n = 116) and patients (n = 115), and a multistakeholder workshop (n = 9). The interviews with and survey of health-care professionals showed that most health-care professionals define steroid resistance as an incomplete response to 40 mg per day of prednisolone after 2 weeks. The survey also found that anti-tumour necrosis factor drugs (particularly infliximab) are the most frequently offered drugs across most steroid-resistant (and steroid-dependent) patient scenarios, but they are less frequently offered to thiopurine-naive patients. Patient interviews identified several factors influencing their treatment choices, including effectiveness of treatment, recommendations from health-care professionals, route of administration and side effects. Over time, depending on the severity and duration of symptoms and, crucially, as medical treatment options become exhausted, patients are willing to try alternative treatments and, eventually, to undergo surgery. The discrete choice experiments found that the probability of remission and of side effects strongly influences the treatment choices of both patients and health-care professionals. Patients are less likely to choose a treatment that takes longer to improve symptoms. Health-care professionals are willing to make difficult compromises by tolerating greater safety risks in exchange for therapeutic benefits. The treatments ranked most positively by patients were infliximab and tofacitinib (each preferred by 38% of patients), and the predicted probability of uptake by health-care professionals was greatest for infliximab (62%). The survey and the discrete choice experiments with patients and health-care professionals are limited by their relatively small sample sizes. The qualitative studies are subject to selection bias. The timing of the different substudies, both before and during the COVID-19 pandemic, is a potential limitation. We have identified factors influencing treatment decisions for steroid-resistant ulcerative colitis and the characteristics to consider when choosing treatments to evaluate in future randomised controlled trials. The findings may be used to improve discussions between patients and health-care professionals when they review treatment options for steroid-resistant ulcerative colitis. This research highlights the need for consensus work to establish an agreed definition of steroid resistance in ulcerative colitis and a greater understanding of the optimal use of tofacitinib and surgery for this patient group. A randomised controlled trial comparing infliximab with tofacitinib is also recommended. This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 41. See the NIHR Journals Library website for further project information.

A Case Report on Steroid Resistant Ulcerative Colitis

Ulcerative colitis is a chronic inflammatory bowel disease that affects the large intestine. It leads to bloody diarrhoea and pain in the lower abdomen. In a 22-year-old man with steroid resistant ulcerative colitis, doctors were faced with an unusual case where he was producing blood. The patient had no medical history of bleeding (except for blood pressure medication two years ago) and had no predisposing diseases or conditions that would explain his non-bloody diarrhoea and rectal bleeding. In this case, doctors needed to find out if this patient had any other causes of bleeding other than ulcerative colitis such as a condition involving their platelets or a vitamin K deficiency, but none were found. Ulcerative colitis is a chronic inflammatory bowel disease that can lead to serious complications. The case study in this article highlights some of these complications which were treated successfully with steroid therapy. Patients may also experience weight loss, malabsorption issues or fatigue as well as complications such as liver problems. The case study also highlights the severity of the patient's condition before diagnosis and treatment, which is why need more research on all cases like this.

Patient preferences for treatment in steroid resistant ulcerative colitis – a discrete-choice experiment

Background and aim Understanding treatment preferences in those patients who are not responding to corticosteroids for ulcerative colitis is important in informing treatment choices. This study aimed to assess the relative importance of treatment characteristics to patients by conducting a discrete-choice experiment. Methods Patients completed the questionnaire online. All data were collected between September and December 2020. Participants were shown 13 discrete-choice experiment tasks – a series of side-by-side comparisons of competing, hypothetical treatment characteristics and asked to select a preferred treatment. Survey responses were analysed using descriptive statistics and regression analyses. Results 115 patients completed the study. Patient preferences were strongest for treatments with a lower chance of side effects, this attribute had the most influence on the choice of treatment patients preferred. The second most important attribute was an improvement in maintaining remission. Conversely, route and frequency of administration were least important on the choice of treatment patients preferred. Respondents were willing to make trade offs and accept treatment benefits to compensate them for receiving a treatment with a less desirable attribute level. Participants were willing to accept a larger benefit of 45% improvement in maintenance of remission to accept a treatment with a higher probability of side effects. The benefit required was smaller with a 10% improvement in remission required to accept a treatment with a lower probability of side effects. Conclusion Quantifying preferences helps to identify and prioritise treatment characteristics that are important to patients. The results highlight the importance of careful discussion of side effects, including the magnitude of risk, using visualisation tools during a patient consultation to support decisions.

P244 Clinician preferences in treating steroid resistant ulcerative colitis: a discrete-choice experiment (DCE) survey

Abstract Background The optimum treatment for steroid resistant ulcerative colitis (SRUC) is not clear and a range of options can be considered. The aim of this study was to quantify the relative importance of different treatment characteristics to clinicians and understand their preferences for benefit-risk trade-offs. Methods A discrete choice experiment (DCE) was conducted in the UK via online survey of clinicians with expertise in inflammatory bowel disease. This involved 12 tasks where respondents selected a preferred treatment option when presented with two competing, hypothetical treatment profiles for a SRUC scenario. Profiles described five treatment characteristics focusing on clinical outcomes and safety, identified from qualitative interviews with clinicians and evidence from systematic reviews. DCE responses were analysed using conditional logistic regressions. Regression coefficients were used to calculate benefit-risk trade-offs, to find the rate at which clinicians are willing to trade levels of risks in exchange for the preferred levels of clinical outcomes. Regression coefficients were also used to predict uptake rates for selected drugs currently prescribed to patients with SRUC. Results 116 clinicians completed the survey (age 46y; female 42%; consultant 60%; nurse 26%; mean experience 11y). Figure 1 shows the treatment characteristics that make respondents more likely (positive coefficient) or less likely (negative coefficient) to choose a treatment. One unit increase in both lymphoma risk and serious infection risk were strongly considered when clinicians were choosing a treatment compared to one unit increase in the symptom improvement characteristics. Clinicians would accept a higher lymphoma risk of 5 per 10,000 patient years for a 10% improvement in remission rate compared to 4 and 2 cases per 10,000 patient years for 10% better rates of clinical response and mucosal healing respectively. Clinicians at secondary hospitals accepted a lymphoma risk of 4 cases per 10,000 patient years for a 10% improvement in remission vs 7 per 10,000 patient years at tertiary centres. Similar trade-off results were found for serious infection risks. Predicted uptake comparing preferred characteristics to existing treatments was infliximab (62%), tofacitinib (18%), vedolizumab (15%) and adalimumab (5%). Conclusion Clinicians are willing to make difficult trade-offs and tolerate elevated safety risks in exchange for therapeutic benefits. Risk tolerance was highest if the treatment improved long term remission rate, lowest for mucosal healing and higher in clinicians at tertiary centres. The results help to better understand treatment decisions and identify outcomes that might be considered in choosing agents to evaluate in clinical trials.

Adrenomedullin for steroid-resistant ulcerative colitis: a randomized, double-blind, placebo-controlled phase-2a clinical trial

BackgroundAdrenomedullin (AM) is a bioactive peptide having many pleiotropic effects, including mucosal healing and immunomodulation. AM has shown beneficial effects in rodent models and in preliminary study for patients with ulcerative colitis (UC). We performed a clinical trial to investigate the efficacy and safety of AM in patients with UC.MethodsThis was a multi-center, double-blind, placebo-controlled phase-2a trial evaluating 28 patients in Japan with steroid-resistant UC. Patients were randomly assigned to four groups and given an infusion of 5, 10, 15 ng/kg/min of AM or placebo for 8 h per day for 14 days. The primary endpoint was the change in Mayo scores at 2 weeks. Main secondary endpoints included the change in Mayo scores and the rate of clinical remission at 8 weeks, defined as a Mayo score 0.ResultsNo differences in the primary or secondary endpoints were observed among the four groups at 2 weeks. Despite the insufficient tracking rate, the Mayo score at 8 weeks was only significantly decreased in the high-dose AM group (15 ng/kg/min) compared with the placebo group (− 9.3 ± 1.2 vs. − 3.0 ± 2.8, P = 0.035), with its rate of clinical remission at 8 weeks being significantly higher (3/3, 100% vs. 0/2, 0%, P = 0.025). We noted mild but no serious adverse events caused by the vasodilatory effect of AM.ConclusionsIn this double-blind randomized trial, we observed the complete remission at 8 weeks in patients with steroid-resistant UC receiving a high dose of AM.Clinical trial registryJAPIC clinical trials information; Japic CTI-205255 (200410115290). https://www.clinicaltrials.jp/cti-user/trial/Search.jsp.

Current Diagnostic and Therapeutic Approaches to Cytomegalovirus Infections in Ulcerative Colitis Patients Based on Clinical and Basic Research Data.

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus (the human herpesvirus 5) and an opportunistic pathogen that primarily infects HIV-positive and other immuno-compromised patients. Retrospective studies in the field of inflammatory bowel disease (IBD) have suggested a relationship between a concomitant colonic HCMV infection and poor outcomes in patients with an ulcerative colitis (UC) due to the presence of HCMV in surgical specimens of patients with a toxic megacolon or a steroid-resistant UC. Therefore, gastroenterologists have focused on the contribution of HCMV infections in the exacerbation of UC. Numerous studies have addressed the benefits of treating colonic HCMV reactivation in UC using an antiviral treatment. However, its clinical relevance remains uncertain as only a few prospective studies have assessed the direct relationship between clinical outcomes and the viral load of HCMV in colonic tissues. HCMV reactivation can be triggered by inflammation according to fundamental research studies. Thus, optimal control of intestinal inflammation is essential for preventing an HCMV reactivation in the intestinal mucosa. Indeed, several reports have indicated the effectiveness of an anti-tumor necrosis factor-alpha (TNFα) treatment in patients with an active UC and concomitant HCMV infections. In this review, we describe the mechanism of HCMV reactivation in UC cases and discuss the current issues regarding diagnosis and treatment of HCMV infections in UC patients.

Patient views about the impact of ulcerative colitis and its management with drug treatment and surgery: a nested qualitative study within the CONSTRUCT trial

BackgroundA nested qualitative interview study within the CONSTRUCT trial was conducted to explore experiences and perceptions of patients with acute severe ulcerative colitis following treatment with infliximab or ciclosporin, surgery, or other medication.MethodsTwo hundred seventy patients with steroid-resistant ulcerative colitis were randomised to either infliximab or ciclosporin. Interviews were conducted with 20 trial participants. Thirty-five data capture events took place in total, 20 interviews conducted 3 months after treatment and a further 15 interviews with the same cohort as second interviews at 12 months.ResultsDisease duration varied but similar stories emerged about how people adjusted to living with ulcerative colitis. Issues raised by patients included; the debilitating effect of the disease on quality of life, living with the unpredictability of symptoms and treatment, dealing with embarrassment and stigma and the desire to share knowledge of the disease with others to combat the private nature of this debilitating illness and bring greater visibility to patient experience of symptoms and outcomes.ConclusionPatients were more positive about treatment with infliximab than ciclosporin, mainly due to the cumbersome intravenous regimen required for ciclosporin. Prompt diagnosis is required and early reporting of changes in symptoms is encouraged to ensure appropriate treatment.Trial registrationThis trial is registered with the ISRCTN registry; number ISRCTN22663589. The date of registration was 16/05/2008.

Infliximab versus cyclosporine for severe ulcerative colitis refractory to steroids: A protocol for systematic review and meta-analysis.

Background:Infliximab and cyclosporine are two main therapies in treating acute severe ulcerative colitis (ASUC), our objective is to assess the effectiveness and safety of cyclosporine (CSA) versus infliximab (IFX) as rescue agents in patients with steroid-refractory ulcerative colitis (UC).Methods:We will search three databases from inception to May 2018, and 19 studies are identified that infliximab and cyclosporine as a treatment in steroid-refractory UC patients. The primary outcome was short-term response to treatment. Secondary outcomes included the rates of colectomy at 3 months, 12 months, 36 months, adverse drug reactions and mortality in those who received rescue therapy.Results:This update review will provide a high quality synthesis of current evidence of two treatment for steroid-refractory ulcerative colitis. The definition of severe colitis is according to Truelove and Witts’ criteria.Conclusions:In the treatment of steroid-resistant ulcerative colitis with infliximab and cyclosporine, there is no difference between the two treatments on short-term and long-term results.

Combination Antibiotics Improves Disease Activity and Alters Microbial Communities in Children With Ulcerative Colitis.

Combinations of antibiotics have shown promise in off-label treatment of Inflammatory Bowel Disease (IBD) flares in adult and pediatric patients1–6. In a small pediatric cohort of moderate-severe medically refractory Ulcerative Colitis (UC), half achieved remission with a regimen of 3–4 antibiotics6. The rationale is to decrease mucosal inflammation by altering intestinal microbiota, however, to date no study has documented these changes. We report our experience with combination oral antibiotics in symptomatic pediatric patients with steroid-dependent or -resistant UC, and demonstrate significant alterations in gut microbiota during and after antibiotic therapy with reductions in inflammatory markers.

330 - Combination Therapy of Cyclosporine and Vedolizumab is Effective and Safe for Severe, Steroid-Resistant Ulcerative Colitis Patients: A Prospective Study

330 - Combination Therapy of Cyclosporine and Vedolizumab is Effective and Safe for Severe, Steroid-Resistant Ulcerative Colitis Patients: A Prospective Study

DOP049 Combination therapy of cyclosporine and vedolizumab is effective and safe for severe, steroid-resistant ulcerative colitis patients: A prospective study

DOP049 Combination therapy of cyclosporine and vedolizumab is effective and safe for severe, steroid-resistant ulcerative colitis patients: A prospective study

Validation of the Crohn's and Ulcerative Colitis questionnaire in patients with acute severe ulcerative colitis.

The Crohn's and Ulcerative Colitis questionnaire (CUCQ) has previously been validated in patients with mild to moderate Crohn's and ulcerative colitis (UC). The aim of this study was to validate the tool in patients with acute severe UC. We undertook a validation of the CUCQ in patients recruited to the COmparison of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis Trial (CONSTRUCT). We carried out psychometric analysis to examine the underlying dimensions of the scale, internal consistency and construct validity. We carried out stepwise regression to examine which items accounted for the greatest variance in the scale. We obtained complete data for 270 patients. The internal consistency of the CUCQ was excellent (Cronbach's alpha > 0.8). The CUCQ scores achieved significant correlations with two generic quality of life scales (SF-12 and EQ-5D), demonstrating good construct validity. Stepwise regression identified 16 items that accounted for greater than 95% of the variance of the CUCQ. Only three of the eight items selected for a short form in mild to moderate patients were selected for patients with acute severe UC. The CUCQ demonstrated good validity in our sample of acute severe UC patients. Stepwise regression identified potential to shorten the tool, but that different items would be selected compared with less severe patients. If the tool is to be applied across the spectrum of disease it would be more appropriate to use the full 32 items in the scale. Further work to explore test-retest is required in acute patients.

Healthcare professionals’ views of the use and administration of two salvage therapy drugs for acute ulcerative colitis: a nested qualitative study within the CONSTRUCT trial

ObjectivesInsight into healthcare professionals’ views and experiences of the use of ciclosporin and infliximab as salvage therapies for acute ulcerative colitis (UC) and how this may affect participation in a...

Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: pragmatic randomised Trial and economic evaluation (CONSTRUCT)

The efficacy of infliximab and ciclosporin in treating severe ulcerative colitis (UC) is proven, but there has been no comparative evaluation of effectiveness. To compare the clinical effectiveness and cost-effectiveness of infliximab and ciclosporin in treating steroid-resistant acute severe UC. Between May 2010 and February 2013 we recruited 270 participants from 52 hospitals in England, Scotland and Wales to an open-label parallel-group, pragmatic randomised trial. Consented patients admitted with severe colitis completed baseline quality-of-life questionnaires before receiving intravenous hydrocortisone. If they failed to respond within about 5 days, and met other inclusion criteria, we invited them to participate and used a web-based adaptive randomisation algorithm to allocate them in equal proportions between 5 mg/kg of intravenous infliximab at 0, 2 and 6 weeks or 2 mg/kg/day of intravenous ciclosporin for 7 days followed by 5.5 mg/kg/day of oral ciclosporin until 12 weeks from randomisation. Further treatment was at the discretion of physicians responsible for clinical management. The primary outcome was quality-adjusted survival (QAS): the area under the curve (AUC) of scores derived from Crohn's and Ulcerative Colitis Questionnaires completed by participants at 3 and 6 months, and then 6-monthly over 1-3 years, more frequently after surgery. Secondary outcomes collected simultaneously included European Quality of Life-5 Dimensions (EQ-5D) scores and NHS resource use to estimate cost-effectiveness. Blinding was possible only for data analysts. We interviewed 20 trial participants and 23 participating professionals. Funded data collection finished in March 2014. Most participants consented to complete annual questionnaires and for us to analyse their routinely collected health data over 10 years. The 135 participants in each group were well matched at baseline. In 121 participants analysed in each group, we found no significant difference between infliximab and ciclosporin in QAS [mean difference in AUC/day 0.0297 favouring ciclosporin, 95% confidence interval (CI) -0.0088 to 0.0682; p = 0.129]; EQ-5D scores (quality-adjusted life-year mean difference 0.021 favouring ciclosporin, 95% CI -0.032 to 0.096; p = 0.350); Short Form questionnaire-6 Dimensions scores (mean difference 0.0051 favouring ciclosporin, 95% CI -0.0250 to 0.0353; p = 0.737). There was no statistically significant difference in colectomy rates [odds ratio (OR) 1.350 favouring infliximab, 95% CI 0.832 to 2.188; p = 0.223]; numbers of serious adverse reactions (event ratio = 0.938 favouring ciclosporin, 95% CI 0.590 to 1.493; p = 0.788); participants with serious adverse reactions (OR 0.660 favouring ciclosporin, 95% CI 0.282 to 1.546; p = 0.338); numbers of serious adverse events (event ratio 1.075 favouring infliximab, 95% CI 0.603 to 1.917; p = 0.807); participants with serious adverse events (OR 0.999 favouring infliximab, 95% CI 0.473 to 2.114; p = 0.998); deaths (all three who died received infliximab; p = 0.247) or concomitant use of immunosuppressants. The lower cost of ciclosporin led to lower total NHS costs (mean difference -£5632, 95% CI -£8305 to -£2773; p < 0.001). Interviews highlighted the debilitating effect of UC; participants were more positive about infliximab than ciclosporin. Professionals reported advantages and disadvantages with both drugs, but nurses disliked the intravenous ciclosporin. Total cost to the NHS was considerably higher for infliximab than ciclosporin. Nevertheless, there was no significant difference between the two drugs in clinical effectiveness, colectomy rates, incidence of SAEs or reactions, or mortality, when measured 1-3 years post treatment. To assess long-term outcome participants will be followed up for 10 years post randomisation, using questionnaires and routinely collected data. Further studies will be needed to evaluate the efficacy and effectiveness of new anti-tumour necrosis factor drugs and formulations of ciclosporin. Current Controlled Trials ISRCTN22663589. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 44. See the NIHR Journals Library website for further project information.

Patient and health professionals’ perspectives on the use of ciclosporin and infliximab when treating acute severe ulcerative colitis: an added dimension to the construct trial

Aim The COmparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis Trial (CONSTRUCT) aimed to compare the clinical and cost effectiveness of infliximab and ciclosporin in the treatment of steroid resistant acute severe ulcerative colitis, using quantitative, qualitative, and health economic data. The qualitative element explored patients’ and health professionals’ views of the two drugs.

Randomised controlled trial. Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: Trial design and protocol (CONSTRUCT)

IntroductionMany patients with ulcerative colitis (UC) present with acute exacerbations needing hospital admission. Treatment includes intravenous steroids but up to 40% of patients do not respond and require emergency colectomy....

Clinical significance of cytomegalovirus infection in patients with inflammatory bowel disease

Cytomegalovirus (CMV) infection is common in humans. The virus then enters a "latency phase" and can reactivate to different stimuli such as immunosuppression. The clinical significance of CMV infection in inflammatory bowel disease is different in Crohn's disease (CD) and ulcerative colitis (UC). CMV does not interfere in the clinical course of CD. However, CMV reactivation is frequent in severe or steroid-resistant UC. It is not known whether the virus exacerbates the disease or simply appears as a bystander of a severe disease. Different methods are used to diagnose CMV colitis. Diagnosis is classically based on histopathological identification of viral-infected cells or CMV antigens in biopsied tissues using haematoxylin-eosin or immunohistochemistry, other tests on blood or tissue samples are currently being investigated. Polymerase chain reaction performed in colonic mucosa has a high sensitivity and a positive result could be associated with a worse prognosis disease; further studies are needed to determine the most appropriate strategy with positive CMV-DNA in colonic mucosa. Specific endoscopic features have not been described in active UC and CMV infection. CMV colitis is usually treated with ganciclovir for several weeks, there are different opinions about whether or not to stop immunosuppressive therapy. Other antiviral drugs may be used. Multicenter controlled studies would needed to determine which subgroup of UC patients would benefit from early antiviral treatment.

P355 Efficacy and safety of oral tacrolimus for the treatment of severe steroid-resistant ulcerative colitis

Background: Ulcerative colitis (UC) that occurs in childhood is usually an extensive colitis or pancolitis and is most often associated with severe steroid-refractory flares. Tacrolimus is a second-line drug therapy indicated in patients with severe flare that is unresponsive to steroid therapy. Objective: to describe our experience of the efficacy and safety of oral tacrolimus treatment in children with steroid-resistant severe ulcerative colitis. Methods: We conducted a retrospective study that included all patients under 18 years suffering from serious flares of ulcerative colitis treated with oral tacrolimus during the period between January 1998 and October 2011. All patients received an oral dose of 0.12mg/kg/day. The drug dosage was adjusted to achieve a plasma trough level of tacrolimus between 5 and 10 ng/mL. For statistical analysis and preparation of the survival curves we used the SPSS version 17.0 for Windows program. A p value <0.01 was considered as significant. Results: A total of 10 patients, 7 women were included. Seven patiens were in their first attack of the disease. The mean age was 9.4±4.9 years-old, and the time course of the disease of 1.3 months (IQR, 1 to 5.7m). The initial clinical response was achieved in 6 patients. All nonresponders required colectomy within one month after initiation of treatment. In the subgroup that responded initially, 2 of 6 patients required colectomy, one at 10 months after starting treatment and the other one at 6 years and 4 months after the immunomodulatory therapy was stopped. Plasma trough levels of tacrolimus were 4 13 ng/ml. The median duration of treatment in the responder group was 4.7 months (IQ, 3.7 to 6) versus 0.23 months in the nonresponders (IQ 0.13 to 0.8m), p = 0.01. Tacrolimus was well tolerated in all cases. Conclusions: Tacrolimus is useful in inducing remission in patients with acute, severe steroid-resistant flares of ulcerative colitis. It can change the course of the disease, and it can prevent or delay surgery allowing to prepare the patient and his family for a probable surgery.

Update on the Management of Ulcerative Colitis

The treatment options for inflammatory bowel disease have expanded with the introduction of biological therapies. Recently published controlled clinical trials were searched and those that impact the clinical management of ulcerative colitis (UC) are discussed in this review. In the management of mild to moderate UC, mesalamine still remains the first choice of drug. The newly developed once daily formulations have shown equal efficacy to divided doses and possibly portend better compliance owing to a simplified regimen. In outpatients with moderate to severe UC, recent data indicate that infliximab induced and maintained remission leads to decreased colectomy rates and fewer hospitalizations. An alternative anti-tumor necrosis factor (TNF) agent, adalimumab, was also recently shown to be effective for induction of remission in moderate to severe UC. The use of immunosuppressives, such as azathioprine and mercaptopurine, is associated with decreased colectomy rates and thioguanine was shown to be effective in maintaining clinical remission in those who are intolerant to azathioprine/mercaptopurine. In hospitalized patients with steroid resistant severe UC, infliximab and tacrolimus may be alternatives to cyclosporine in those who are otherwise candidates for colectomy. Adequate long-term maintenance therapy with immunosuppressives or anti-TNF therapy is required after rescue therapy for a sustained benefit. Future research is needed to position the available anti-TNF agents and combined immunosuppressive therapy in the treatment of UC to achieve and maintain steroid free remission.