Treatment Of Steroid-refractory Ulcerative Colitis Research Articles

Analysis of the Clinical Efficacy of Infliximab in the Treatment of Steroid-Refractory Ulcerative Colitis in Children

Background: Incidence of ulcerative colitis (UC) in children has increased worldwide. Objectives: In the current study, we summarized our clinical experience using infliximab (IFX) in the treatment of children with steroid-refractory UC. Methods: The clinical data of 9 steroid-refractory UC patients with average age of 8 years who were treated with IFX in our hospital were analyzed. Results: At the end of the induction period, 6 achieved a clinically significant response. Of the 6 children, 4 had mucosal healing and 2 had endoscopic remission. At week 30, among the 6 children who achieved a clinically significant response, 3 had persistent clinical remission and mucosal healing, 1 achieved mucosal healing from endoscopic remission, 1 had mild disease, and the other child had not reached 30 weeks of treatment as of this writing. At week 54, 6 of 9 children achieved clinical remission and 5 had mucosal healing. The hemoglobin concentration in the children who achieved a clinically significant response was higher than pre-treatment and the inflammation markers were lower than pre-treatment. During IFX treatment, five children had a loss of response, three had a primary non-response, and two had a secondary non-response. The latter children achieved clinical remission with optimized treatment. Conclusions: IFX is a salvage treatment option for children with moderate-to-severe steroid-refractory UC. The course of treatment and the timing of drug withdrawal warrants further study.

German S3-Guideline on the treatment of Psoriasis vulgaris, adapted from EuroGuiDerm - Part 2: Treatment monitoring and specific clinical or comorbid situations.

German S3-Guideline on the treatment of Psoriasis vulgaris, adapted from EuroGuiDerm - Part 2: Treatment monitoring and specific clinical or comorbid situations.

Tacrolimus Therapy in Steroid-Refractory Ulcerative Colitis: A Review.

Inflammatory bowel diseases are known for a chronic inflammatory process of the gastrointestinal tract and include Crohn's disease and ulcerative colitis (UC). Patients who are dependent on or resistant to corticosteroids account for about 20% of severe UC patients. Tacrolimus is a calcineurin inhibitor that has recently been used in the treatment of steroid-refractory ulcerative colitis. Tacrolimus has been demonstrated to have remarkable therapeutic efficacy in UC patients, without increased risk of severe adverse effects such as induction of remission and maintenance therapy. This article reviews the mechanism of action, pharmacogenetics, efficacy, and safety of tacrolimus for patients with steroid-refractory 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,

Protocolo de diagnóstico y tratamiento de la colitis ulcerosa grave corticorrefractaria

Introduction.It is defined as severe outbreak of ulcerative colitis refractory cortico one in which no response after 3-5 days of treatment with 60mg / day of methylprednisolone intravenously observed. Clinical management.In this situation, they exclude reversible causes of refractoriness to steroids and plan the rescue medical treatment, bearing in mind the surgical option. Medical treatment.Both cyclosporine and infliximab have proven effective in the treatment of steroid-refractory ulcerative colitis. The choice of either drug will depend on individual patient characteristics, treatment base to take before the outbreak and the circumstances of the hospital. Surgical treatment.In general, in the case of failure of the first medical rescue treatment chosen performing colectomy is recommended. Sequential treatment of cyclosporine and infliximab can be effective, avoiding colectomy in some cases. However, this strategy is associated with an increased risk of complications, so it should be reserved for selected patients in referral centers.

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.

ABCB1 Single-Nucleotide Polymorphisms Determine Tacrolimus Response in Patients With Ulcerative Colitis

Tacrolimus (Tac) is effective in the treatment of steroid-refractory ulcerative colitis (UC); however, nonresponse and unpredictable side effects are major limitations. Because Tac response in patients who have undergone solid-organ transplantation has been associated with the presence of variants in CYP3A and ABCB1, we elucidated the contributions of CYP3A4*1B and CYP3A5*3 and of ABCB1 1236C>T, 2677G>T,A, and 3435C>T polymorphisms to Tac response in 89 patients with UC. Short-term remission and response were achieved in 61 and 14% of the patients, respectively, and were associated with colectomy-free survival. In a linear logistic regression model, patients with homozygous variants for one of the three ABCB1 alleles showed significantly higher short-term remission rates as compared with those of other genotypes. The effects held true after multivariate analysis including multiple comparisons and were more pronounced after correction for dose-adjusted Tac blood trough levels. We suggest that ABCB1, but not CYP3A5, may predict short-term remission of Tac in steroid-refractory UC.

Cyclosporine treatment of steroid-refractory ulcerative colitis during pregnancy

Cyclosporine is considered a safe and effective treatment of severe steroid-refractory ulcerative colitis (UC). However, few data are available concerning its safety profile in pregnant women. We report here the experience of 5 GETAID centers. In a retrospective study data on patients with severe UC treated with cyclosporine during pregnancy were extracted from medical records of consecutive patients treated between 2001 and 2007. Eight patients (median age 30.5 years old) were identified. At the time of flare-up the median duration of pregnancy was 11.5 weeks of gestation (range 4-25). Seven patients had pancolitis. All patients had more than 3 commonly used clinical and biological severity criteria. Three patients had severe endoscopic lesions and 5 patients had not. All patients received intravenous corticosteroids for at least 7 days before introduction of cyclosporine. Two patients received azathioprine during treatment with cyclosporine. No severe infections or other complications due to treatment were observed. Treatment was effective in 7/8 patients. One patient received infliximab due to cyclosporine therapy failure with a good outcome. No colectomy was performed during pregnancy. Seven pregnancies were conducted to term, but 1 in utero death occurred due to maternal absence of S-protein. Two newborns were premature, including 1 case of hypotrophy. No malformations were observed. In our experience, treatment with cyclosporine for steroid-refractory UC during pregnancy can be considered safe and effective.

Visilizumab shows promise for the treatment of steroid-refractory ulcerative colitis

Visilizumab shows promise for the treatment of steroid-refractory ulcerative colitis

Thrombin generation in mesalazine refractory ulcerative colitis and the influence of low molecular weight heparin

In ulcerative colitis (UC), a state of hypercoagulation has frequently been observed. Low molecular weight heparin (LMWH) has shown beneficial effects as an adjuvant treatment of steroid refractory UC in open trials. We assessed potential therapeutic effects of the LMWH reviparin in hospitalised patients with mesalazine refractory UC, as well as its influence on haemostasis factors. Twenty-nine patients with mild-to-moderately active UC were included in a double-blind placebo controlled trial. All patients had a flare-up of disease under mesalazine treatment. Reviparin (Clivarin) 3,436 IU anti-Xa/0.6 ml or placebo s.c. was added, and self-administered twice daily for 8 weeks. Patients were monitored for possible adverse events and changes in clinical symptoms. Endoscopical, histological, biochemical and haemostasis parameters were analysed. Tolerability and compliance were excellent and no serious adverse events occurred. No significant differences were observed on the clinical, endoscopical and histological outcome, as compared to placebo. A high intrinsic and extrinsic thrombin potential was found before LMWH therapy. However, the significant reduction in the thrombin generation by LMWH was not related to the reduction in disease activity. The LMWH reviparine reduces thrombin generation in patients with mild-to-moderately active, mesalazine refractory UC, but is not associated with a reduction in disease activity.

Cytomegalovirus infection in severe ulcerative colitis patients undergoing continuous intravenous cyclosporine treatment in Japan

To investigate active cytomegalovirus (CMV) infection following the cyclosporine A (CyA) treatment of steroid-refractory ulcerative colitis (UC). Twenty-three patients with severe UC not responding to steroid therapy (male 14, and female 9) enrolled at Nagoya University Hospital from 1999 to 2005. They received continuous intravenous infusion of CyA (average 4 mg/kg per day) for 1 mo. Serum and colonic biopsy samples were collected before CyA treatment and 4 d, 10 d, 20 d, and 30 d after treatment. Patients were evaluated for CMV by using serology (IgM antibody by ELISA), quantitative real-time PCR for CMV DNA, and histopathological assessment of hematoxylin and eosin (HE)-stained colonic biopsies. CMV infection was indicated by positive results in any test. No patients had active CMV infection before CyA treatment. Eighteen of 23 UC patients treated with CyA were infected with active CMV (IgM antibody in 16/23 patients, 69.6%; CMV DNA in 18/23 patients, 78.2%; and inclusion bodies in 4/23 patients, 17.3%). There was no difference in the active CMV-infection rate between males and females. Active CMV infection was observed after approximately 8 d of CyA treatment, leading to an exacerbation of colitis. Fifteen of these 18 patients with active CMV infection (83.3%) required surgical treatment because of severe deteriorating colitis. Treatment with ganciclovir rendered surgery avoidable in three patients. Our results suggest that active CMV infection in severe UC patients treated with CyA is associated with poor outcome. Further, ganciclovir is useful for treatment of CMV-associated UC after immuno-suppressive therapy.

Infliximab for acute severe ulcerative colitis: A randomized pilot study in non steroid refractory patients

Background: Steroids comprise the standard therapy for acute severe ulcerative colitis Therapeutic alternatives for patmms in whom steroids would usually be contraindicated are rare. Drugs such as cyclosporine and tacrolimus have a considerable risk of nephrotoxicity, and immunosuppressams, such as azathioprine have a delayed onset of effectivity. The chimene monoclonal antibody to tumor necrosis factor alpha, lnfliximab, seems to be effective in the treatment of steroid-refractory ulcerative colitis. We, therefore, evaluated whether Infliximab can achieve remission in non steroid refractory patients with acute severe ulcerative pancolitis in a randomized, prednisolone-controlled pilot trial over 3 months. Methods: Patients were elegible if they had acute severe disease with a modified Truelove and Wilts activity score of more than ten for at least two weeks and if they were currently not receiving immunomodulators or more than 10 mg prednisolone per day. Patients were randomly assigned to receive either infliximab or high dose predinsolone with a 50% likelyhood for each. They received either three intravenous infusions of lnfhximab at 5 rag/ kg body weight, at 0, 2 and 6 weeks (group A) or prednisolone 1.5mg/kg body weight, daily for two weeks, followed by lmg/kg for one week, followed by a tapering regimen with a weekly reduction of 5mg (group B). Therapy success was defined as clinical response in terms of a decrease of more than 5 points from baseline score and to less than 10 points total after 3 as well as after 13 weeks. Results: 13 patients (8 women, 5 men) were randomized (6 for group A and 7 for group B). The median baseline activity scores were 13.5 (12 to 18) in group A and 14.0 (11 to 18) in group B. Five of six patients in group A and six of seven patients in group B showed therapy success after three as well as after 13 weeks. One patient in group A showed no response at all and one patient in group B relapsed after eleven weeks. No significant complications or side effects were observed. Conclusion: Infliximab seems to be as effective as high dose prednisolone in the treatment of acute severe ulcerative colitis. The obtained data call for larger controlled trials.

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.

Severe steroid-unresponsive ulcerative colitis: outcomes of restorative proctocolectomy in patients undergoing cyclosporin treatment.

The recent introduction of the immune suppressor cyclosporin for treatment of steroid-refractory ulcerative colitis has required surgeons to perform a colectomy in those patients who eventually fail this rescue treatment, thus raising questions as to the safety of surgery as performed in patients with a heavily manipulated immune system. To assess the rates of mortality and morbidity in this setting, we studied a cohort of consecutive patients who had surgery after failing cyclosporin for refractory ulcerative colitis at our center. Between January 1991 and December 1996, 25 patients with ulcerative colitis underwent restorative proctocolectomy performed in three steps (21 patients) and in two steps (4 patients). Seventeen of the 25 patients (68 percent) were initial nonresponders to a dose of 2 mg/kg/day of intravenous cyclosporin and underwent surgery immediately, the remaining 8 (32 percent) relapsed as outpatients on oral cyclosporin and were readmitted for surgery. There was no operative mortality. Nine patients of the 25 developed postoperative (early) complications (36 percent). The three-step operation subset had a 28 percent complication rate, the two-step 75 percent. Three patients needed reoperation. A total of 11 patients (44 percent) reported with late complications: two patients required surgical treatment, one for obstruction and one for pouch-perianal fistula. Three cases of pouchitis were recorded. No patient required pouch removal. Given the absence of postoperative mortality and a low overall complication rate, restorative proctocolectomy can safely be performed in patients who fail rescue treatment with a dose of 2 mg/kg of cyclosporin for steroid-refractory ulcerative colitis. Corollary evidence in this article hints but does not prove that the three-step procedure is safer than the two-step operation.