Steroid-refractory Acute Severe Ulcerative Colitis Research Articles

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,

P541. Cyclosporine therapy is effective in acute severe steroid-refractory ulcerative colitis

P541. Cyclosporine therapy is effective in acute severe steroid-refractory ulcerative colitis

Early Colectomy in Steroid-Refractory Acute Severe Ulcerative Colitis Improves Operative Outcome

Early Colectomy in Steroid-Refractory Acute Severe Ulcerative Colitis Improves Operative Outcome

Systematic Review: Sequential Rescue Therapy in Severe Ulcerative Colitis: Do the Benefits Outweigh the Risks?

The options for medical management of acute severe steroid-refractory ulcerative colitis (UC) are limited. Recent guidelines recommend against use of sequential rescue therapy in the setting of failed medical management with initial salvage therapy. A systematic review was conducted to assess outcomes of sequential rescue therapy with infliximab (IFX) and calcineurin inhibitors like cyclosporine (CsA) or tacrolimus (Tac) in patients with steroid-refractory UC. A literature search identified studies that investigated treatment with IFX and CsA or Tac in acute severe UC. Outcomes of interest included short-term symptomatic response to treatment, rates of remission, adverse drug reactions, serious infections, mortality, and colectomy at 3 and 12 months. Overall, ten studies with 314 participants were eligible for inclusion. After sequential treatment, patients achieved short-term treatment response in 62.4% (95% confidence interval [CI], 57.0%-67.8%) of cases and remission in 38.9% (95% CI, 33.5%-44.3%). Colectomy rates were 28.3% (95% CI, 21.7%-34.5%) at 3 months and 42.3% (95% CI, 36.0%-48.6%) at 12 months. Adverse events were encountered by 23.0% (95% CI, 17.7%-28.3%) of patients, including serious infections in 6.7% (95% CI, 3.6%-9.8%) and mortality in 1% (95% CI, 0%-2.1%). The risk of sequential therapy in steroid-refractory UC seems lower than initially reported. Caution must be exercised however because of very low-quality evidence. In contrast to recent guidelines, the current analysis does not support a decision for or against use of sequential rescue therapy, which should only be performed at specialized referral centers familiar with the use of calcineurin inhibition.

Management of severe ulcerative colitis.

Acute severe steroid-refractory ulcerative colitis (ASUC) provides challenges for physicians and surgeons who manage these patients. When a patient is diagnosed with ASUC, they should be admitted for inpatient management including intravenous corticosteroids, venous thromboembolism prophylaxis, oral or enteral feeding if tolerated, and exclusion of infection including Clostridium difficile. Failure to improve by day 3 of corticosteroids requires escalation to medical rescue therapies such as infliximab or cyclosporine, or surgical management with colectomy. This chapter will review management of ASUC with a focus on the medical rescue options available.

P-075 YI Systematic Review

The options for medical management of acute severe steroid-refractory ulcerative colitis (UC) are limited. Recent guidelines caution against use of sequential rescue therapy in the setting of failed medical management with an initial salvage therapy. A systematic review was conducted to assess the outcomes of sequential rescue therapy with infliximab (IFX) and calcineurin inhibitors like cyclosporine (CsA) or tacrolimus (Tac) in patients with steroid refractory UC. A literature search identified studies that investigated treatment with IFX and CsA or Tac in acute severe UC. The primary outcome was short term symptomatic response to treatment. Secondary outcomes included adverse drug reactions, serious infections, mortality, rates of remission, and colectomy at 3 months and 12 months. Response rates with 95% confidence intervals (CI) are reported. Overall, 10 studies with 314 participants were eligible for inclusion. After sequential treatment patients achieved short-term treatment response in 62.4% (95% CI, 57.0%–67.8%) of cases and remission in 38.9% (95% CI, 33.5%–44.3%). Colectomy was required in 28.3% (95% CI, 21.7%–34.5%) of patients at 3 months and 42.3% (95% CI 36.0–48.6) at 12 months. Adverse events were encountered by 23.0% (95% CI, 17.7%–28.3%) of patients, including serious infections in 6.7% (95% CI, 3.6%–9.8%) and mortality in 1% (95% CI, 0%–2.1%). Our data summarizing experience from observational studies suggest that the risk-benefit ratio of sequential rescue therapy in acute severe UC seems acceptable. In the setting of failure of corticosteroids and an initial rescue therapy for acute severe UC, consideration can be given to use of another salvage agent based on patient preferences and the safety of this experience from observational data. The sequence of IFX followed by calcineurin inhibitors, or vice versa, have similar treatment outcomes and adverse events. Precautions to minimize the risk of adverse events, including early assessment of treatment response, use of serum drug levels to guide initiation of therapy, and early weaning of concurrent corticosteroids is recommended.

Cyclosporine in steroid refractory acute severe colitis.

Approximately 15-20% patients with ulcerative colitis (UC) suffer from a severe flare during their lifetime which required hospitalization. Intravenous corticosteroids are the first line of therapy for acute severe UC. While almost 70-80% of patients respond to corticosteroids 20% do not. Although colectomy for UC is curative, it has its problems such as increased frequency of stool and pouchitis, which led to search for colon rescue therapy. Cyclosporine and anti-tumor necrosis factor-alpha (anti-TNF á) have emerged as effective colon rescue therapy. While the short-term efficacy of cyclosporine in preventing colectomy is 64-86%, the long-term efficacy is not as good and almost 70% eventually require colectomy over 1-7 years. The efficacy of cyclosporine is equivalent both at a high and low doses and cyclosporine is now used most often as a low dose regime in patients with steroid refractory acute severe UC. Furthermore, recent data suggest that the both cyclosporine and infliximab are equally effective in steroid refractory acute severe UC. Monitoring patients for adverse events and serum cyclosporine levels is mandatory. The response to both cyclosporine and infliximab is rapid and usually occurs within 4-5 days. Despite mounting evidence of its efficacy, cyclosporine remains largely underused because it requires intense monitoring for toxicity especially at higher dosage. Gastroenterologists need to be more familiar with cyclosporine for the management of steroid refractory acute severe UC.

An Accelerated Infliximab Induction Regimen Reduces the Need for Early Colectomy in Patients With Acute Severe Ulcerative Colitis

Administration of infliximab to patients with acute severe ulcerative colitis (ASUC) (rescue therapy) can reduce the rate of early colectomy (within 12 months), but long-term rates of colectomy are the same as those of the pre-biologic era for these patients. The half-life of infliximab is shorter in patients with ASUC than in patients with non-severe UC, so more frequent dosing might be required to produce a therapeutic effect. We performed a retrospective analysis of 50 hospitalized patients who received infliximab for steroid-refractory ASUC at a single academic center from September 2005 through 2013. In 2011 an accelerated dosing strategy for infliximab was introduced; we compared outcomes of standard and accelerated dosing regimens. One group of patients (n= 35) were placed on a standard dosing regimen for infliximab and then given the drug at 0, 2, and 6 weeks and then every 8 weeks thereafter. A second group (n= 15) were placed on an accelerated regimen and received 3 induction doses of infliximab within a median period of 24 days. Rates of colectomy were compared between the groups during induction and follow-up periods. There were no differences between groups in median baseline levels of C-reactive protein, albumin, or hemoglobin. The rate of colectomy during induction therapy was significantly lower with the accelerated regimen (6.7%, 1 of 15) than with the standard regimen (40%, 14 of 35) (Fisher exact test, P= .039). The standard regimen was associated with shorter time to colectomy (log-rank test, P= .042). Among patients who completed induction therapy, subsequent need for colectomy was similar between the groups during the follow-up period. Multivariate analysis showed that factors independently associated with successful induction therapy were level of albumin (g/L) when the treatment began (P= .003) and the accelerated dosing regimen (P= .03). In patients with ASUC, an accelerated infliximab induction strategy reduces the need for early colectomy. An intensified infliximab dosing strategy in response to clinical or laboratory signs of breakthrough inflammation merits consideration in prospective studies.

Tumor Necrosis Factor Alpha Blocking Agents as Treatment for Ulcerative Colitis Intolerant or Refractory to Conventional Medical Therapy: A Meta-Analysis

BackgroundEfficacy of tumor necrosis factor alpha (TNF-α) blockers for treatment of ulcerative colitis that is unresponsive to conventional therapy is unclear due to recent studies yielding conflicting results.AimTo assess the efficacy and safety of anti-TNF-α agents for treatment of ulcerative colitis patients who were intolerant or refractory to conventional medical therapy.MethodsPubmed, Embase, and the Cochrane database were searched. Analysis was performed on randomized controlled trials that assessed anti-TNF-α therapy on ulcerative colitis patients that had previously failed therapy with corticosteroids and/or immunosuppressants. The primary outcome focused on was the frequency of patients that achieved clinical remission. Further trial outcomes of interest included rates of remission without patient use of corticosteroids during the trial, extent of mucosal healing, and the number of cases that resulted in colectomy and serious side effects.ResultsEight trials from seven studies (n = 2122) met the inclusion criteria and were thus included during analysis. TNF-α blockers demonstrated clinical benefit as compared to placebo control as evidenced by an increased frequency of clinical remission (p<0.00001), steroid-free remission (p = 0.01), endoscopic remission (p<0.00001) and a decrease in frequency of colectomy (p = 0.03). No difference was found concerning serious side effects (p = 0.05). Three small trials (n = 57) comparing infliximab to corticosteroid treatment, showed no difference in frequency of clinical remission (p = 0.93), mucosal healing (p = 0.80), and requirement for a colectomy (p = 0.49). One trial compared infliximab to cyclosporine (n = 115), wherein no difference was found in terms of mucosal healing (p = 0.85), colectomy frequency (p = 0.60) and serious side effects (p = 0.23).ConclusionTNF-α blockers are effective and safe therapies for the induction and maintenance of long-term remission and prevention of treatment by colectomy for patients with refractory ulcerative colitis where conventional treatment was previously ineffective. Furthermore, infliximab and cyclosporine were found to be comparable for treating acute severe steroid-refractory ulcerative colitis.

Outcomes of salvage therapy for steroid-refractory acute severe ulcerative colitis: ciclosporin vs. infliximab

Up to 40% of patients who present with acute severe ulcerative colitis (UC) fail to make an adequate response to intravenous corticosteroids. Ciclosporin or infliximab are currently employed as salvage therapy in this clinical scenario. To compare clinical outcomes in patients treated with ciclosporin or infliximab in the setting of steroid-refractory acute severe UC. A prospective study of 83 consecutive presentations of steroid-refractory acute severe UC from 1999 to 2009 was conducted. All study participants satisfied the Truelove and Witts' criteria for acute severe UC. The primary outcome measures were rates of colectomy at discharge from hospital and at 3months and 12months following admission. Eighty-three steroid-refractory acute severe UC events were generated by 83 patients. Salvage therapy was instituted with ciclosporin in 45 patients and infliximab in the remaining 38 patients. Of those patients who received ≥72h of ciclosporin (2-4mg/kg), 56% (24/43) avoided colectomy at the time of discharge, while this figure was 84% (32/38) for those administered one dose of infliximab (5mg/kg) (P=0.006). At 3months, the colectomy-free rate was 53% for ciclosporin (23/43) vs. 76% for infliximab (28/37) (P=0.04), and 42% (18/43) vs. 65% (24/37) at 12months (P=0.04). There were no deaths and two serious adverse events, both occurring in the ciclosporin group. In this large cohort of patients presenting with acute severe UC, we have observed that infliximab salvage therapy is associated with lower rates of both severe adverse events and colectomy than ciclosporin in the short-term and medium-term.

Surgical outcomes in steroid refractory acute severe ulcerative colitis: the impact of rescue therapy

The advent of rescue medical therapy (cyclosporin or infliximab) and laparoscopic surgery has shifted the paradigm in managing steroid refractory acute severe ulcerative colitis (ASUC). We investigated prospectively the impact of rescue therapy on timing and postoperative complications of urgent colectomy and subsequent restorative surgery for steroid refractory ASUC. All consecutive presentations of steroid refractory ASUC at the Royal Brisbane Hospital (1996-2009) were entered in the study. Data collated included demographics, clinical and laboratory parameters on admission, medical therapy and operative and postoperative details. Steroid refractory ASUC patients undergoing immediate colectomy were compared with those failing rescue therapy and requiring same admission colectomy. Of 108 steroid refractory ASUC presentations, 19 (18%) received intravenous steroids only and proceeded directly to colectomy. Rescue medical therapy was instituted in 89 (82%) patients with 30 (34%) failing to respond and proceeding to colectomy. There was no significant difference in the median time from admission to colectomy for rescue therapy compared with steroid-only cases (12 vs 10 days, P = 0.70) or 30-day complication rates (27%vs 47%, P = 0.22). The interval from colectomy to a subsequent restorative procedure was significantly longer for patients who failed rescue therapy (12 vs 5 months, P = 0.02). Furthermore 30-day complications following pouch surgery were significantly higher in patients who failed rescue therapy (32%vs 0%, P = 0.01). Rescue therapy in steroid refractory ASUC is not related to delay in urgent colectomy or increased post-colectomy complications.

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

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. 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. 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. 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.

Infliximab or cyclosporine for acute severe ulcerative colitis: A retrospective analysis

Medical treatment of steroid-refractory ulcerative colitis (UC) is limited to either cyclosporine or infliximab. Studies comparing cyclosporine with either placebo or intravenous methylprednisone showed promise for cyclosporine, but associated it with significant toxicity. There is conflicting, but increasingly positive evidence for using infliximab. There are no studies directly comparing these two treatments. Our aim was to compare the outcomes of patients with steroid-refractory UC treated with either intravenous cyclosporine or infliximab. We carried out a retrospective review of inpatients with steroid-refractory UC, treated with either intravenous cyclosporine or infliximab, at Waitemata District Health Board, between January 2001 and February 2010. The primary end-points were time to colectomy, and colectomy rates at 3 and 12 months. Secondary end-points were time to discharge from initiation of treatment, steroid dependence at 12 months, and reported adverse events. The total study population was 38, with 19 in the infliximab group. Follow up to 12 months was complete in all patients. At 3 months, the colectomy rate was 63% for cyclosporine, compared to 21% (P = 0.0094). By 12 months the rate was 68% and 37% for cyclosporine and infliximab, respectively (P = 0.06). Patients in the cyclosporine group required an additional 5 days in hospital (P = 0.0086). Steroid dependence at 12 months was 50% for cyclosporine versus 25% for infliximab (P = 0.36). Cyclosporine caused more adverse events (P = 0.17). Infliximab improved clinical outcomes compared to the previous use of intravenous cyclosporine in patients admitted with steroid-refractory acute severe UC.

P330 Cyclosporin A as rescue therapy for steroid-refractory acute severe ulcerative colitis: Oral administration is as effective as intravenous

P330 Cyclosporin A as rescue therapy for steroid-refractory acute severe ulcerative colitis: Oral administration is as effective as intravenous

Infliximab rescue therapy for steroid refractory acute severe ulcerative colitis in the exeter ibd cohort

IntroductionInfliximab (IFX) has been shown to be efficacious in the treatment of steroid refractory acute severe ulcerative colitis (ASUC) with reduced rates of colectomy at index admission and at 3-year...

Outcomes of salvage therapy for acute severe ulcerative colitis: Cyclosporin versus Infliximab

Acute severe ulcerative colitis (ASUC) is a common and serious complication of UC. For those cases refractory to intravenous steroid therapy Cyclosporin or, more recently, Infliximab therapy is the current standard of care. Although there have been no published studies comparing and contrasting these agents, clinical experience has previously indicated their effectiveness to be equable in this clinical context. A prospective study of 72 consecutive presentations of steroid refractory ASUC at the Royal Brisbane and Women's Hospital (RBWH) from 1996-2009 was con-ducted to assess the relative efficacy of Cyclosporin and Infliximab in this clinical setting. All study participants satisfied the Truelove and Witts criteria for acute severe colitis (≥6 bloody stools/day with one or more of the following: temperature >37.8°C; pulse rate >90/min; haemoglobin <10.5g/dl; or erythrocyte sedimentation rate (ESR) >30mm/hr) and were prevalent or incident cases of ulcerative colitis as confirmed by histological analysis. Primary endpoints measured were: outcome at discharge and outcome at 12 months after discharge; specifically whether these cases proceeded to total colectomy or were amenable to continuing medical management. The 72 steroid refractory acute colitis events were generated by 68 UC patients from north Brisbane, Queensland. Salvage therapy was instituted with either Cyclosporin in 44(61%) cases or Infliximab in the remaining 28(39%) patients. Of those patients who received Cyclosporin 52% (23/44) proceeded to total colectomy before discharge while this figure was only 18% (5/28) for those administered Infliximab as a salvage therapy. This finding was found to be statistically significant (p = 0.003). Twelve month follow-up data are currently available for 69/72 cases. At this timepoint 68% (30/44) and 44% (11/25) of cases treated with Cyclosporin and Infliximab, respectively, had required surgery for recurrent severe disease (p = 0.049). This study is of significance because it presents longitudinal outcomes data from a large, prospectively studied series of patients with refractory acute severe UC, selected on the basis of validated severity criteria. While it is clear that Infliximab salvage therapy is more efficacious than Cyclosporin in the short term in avoiding surgical intervention, the significance and duration of this benefit remain to be conclusively evaluated. We recognise that a randomised controlled trial is in progress in the United Kingdom that has been designed to answer this question and we await its findings.

Treatment of choice for acute severe steroid-refractory ulcerative colitis is colectomy

Treatment of choice for acute severe steroid-refractory ulcerative colitis is colectomy

Treatment of choice for acute severe steroid-refractory ulcerative colitis is Remicade

Treatment of choice for acute severe steroid-refractory ulcerative colitis is Remicade

Treatment of choice for acute severe steroid-refractory ulcerative colitis is cyclosporine

Treatment of choice for acute severe steroid-refractory ulcerative colitis is cyclosporine