A controlled randomized trial of budesonide versus prednisolone retention enemas in active distal ulcerative colitis

Sixty-four patients with active distal ulcerative colitis participated in a multicentre, randomized, investigator-blind trial to compare the effect of budesonide enema, 2 mg/100 ml, with prednisolone disodium phosphate enema, 31.25 mg/100 ml. Budesonide is a new potent corticosteroid with a rapid first-pass elimination. The patients were treated for 4 weeks, and the efficacy of the drugs were evaluated by sigmoidoscopy, histology, and subjective symptoms after 2 and 4 weeks. After 4 weeks of treatment 16 of 31 patients (52%) receiving budesonide enema had healed endoscopically, compared with 8 of 33 (24%) (p = 0.045) receiving prednisolone enema. Budesonide was superior to prednisolone in terms of both significantly improved sigmoidoscopic and histologic scores and subjective symptoms evaluated by visual analogue scales. The patients receiving prednisolone had a significant depression of endogenous cortisol levels during the treatment period, but not the patients receiving budesonide. Budesonide enema seems to be a promising therapy for active distal ulcerative colitis and causes no adverse reactions.     

Oral prednisolone metasulphobenzoate in the treatment of active ulcerative colitis

BACKGROUND: Corticosteroids are one of the mainstays of treatment for active ulcerative colitis, but they are associated with numerous side effects. The sparingly absorbed corticosteroid prednisolone metasulphobenzoate is used topically in the treatment of distal disease. A targeted-release oral preparation (Predocol) has been developed to allow delivery of this drug to the whole colon. We have studied the effect of oral Predocol on inflammation as measured by 99Tc(m)-HMPAO leucocyte scintigraphy in patients with symptomatic and sigmoidoscopic relapse of known extensive ulcerative colitis. METHODS: Fourteen patients were recruited and received Predocol 47.1 mg twice daily, 8 for 7 days and 6 for 14 days. Scintigraphy was performed prior to and at the end of treatment. Each segment of colon was graded (0-4) and individual scores summed to give a total scintigraphic score. RESULTS: Total scintigraphic score improved by a mean of 2.5 (P = 0.027). Mean individual scores improved in the rectum by 0.7 (P = 0.038) and in the descending colon by 0.8 (P = 0.033). CONCLUSIONS: Predocol is an oral preparation of a poorly absorbed salt of prednisolone that is effective in reducing inflammation over short treatment periods in patients with active ulcerative colitis.     

Methylprednisolone acetate versus oral prednisolone in moderately active ulcerative colitis.

BACKGROUND: Patients with active ulcerative colitis are treated with corticosteroids. We compared the efficacy and safety of intramuscular depot preparation of methylprednisolone acetate with oral prednisolone in the treatment of moderately active ulcerative colitis. DESIGN: Open labeled, randomized, prospective, four-month study. METHODS: 40 patients with moderately active ulcerative colitis (activity index 150-220) were randomized into two groups. Group A (n=21) received methylprednisolone acetate (80 mg intramuscularly once weekly for 6 weeks). Group B (n=19) received oral prednisolone (40 mg/day) in a 'tailing-off' regimen. In addition, patients in both the groups received sulfasalazine. Patients were followed up at 1, 2, 3, 4, 8, 12 and 16 weeks. The primary measure of therapeutic response was activity index. An index of <150 was considered as clinical remission. Secondary efficacy was assessed by subjective evaluation of acceptability of treatment by the patient. RESULTS: After one week of treatment, the decrease in mean activity index was significantly more with oral prednisolone (p<0.05), and five 5 patients (23.8%) in Group A and 12 (63.2%) in Group B were in clinical remission (p<0.05). However, after 2 weeks and beyond, the mean activity index and the number of patients with clinical remission were comparable in the two treatment groups. CONCLUSIONS: Methylprednisolone acetate as a depot preparation and oral prednisolone are equally effective in inducing remission in patients with moderately active ulcerative colitis. Though symptomatic improvement is quicker with oral prednisolone, the remission rate with the two drugs was similar after 2 weeks of treatment.     

Adsorptive granulocyte and monocyte apheresis versus prednisolone in patients with corticosteroid-dependent moderately severe ulcerative colitis

BACKGROUND/AIM: Active ulcerative colitis (UC) is often associated with increased peripheral granulocytes and monocytes/macrophages which show activation behavior and prolonged survival time. Further, mucosal granulocyte level parallels intestinal inflammation and can predict UC relapse. Accordingly, our aim was to see if adsorptive granulocyte/monocyte apheresis (GMA) can promote remission and spare steroid in patients with steroid-dependent (SD) UC. METHODS: 69 SD patients, at the time of relapse, were randomly assigned to groups I (n = 46) and II (n = 23). The mean dose of prednisolone (PSL) was 12 mg/day/patient, CAI (clinical activity index) 9.2 in both groups. Group I patients were given up to 11 GMA sessions over 10 weeks with Adacolumn; in group II, the mean dose of PSL was increased to 30 mg/day/patient. RESULTS: At week 12, 83% of group I and 65% of group II patients were in remission, CAI in group I was 1.7 (p < 0.001) and in group II, 2.5 (p < 0.001). Further, during the 12 weeks of treatment, the cumulative amount of PSL received per patient was 1,157 mg in group I and 1,938 mg in group II (p = 0.001). CONCLUSIONS: GMA appeared to be an effective adjunct to standard drug therapy of moderately severe UC by promoting remission and sparing steroids.     

Oral budesonide therapy for ulcerative colitis: A topical tale

This article has no abstract. To view the article, select the "View Print Version (PDF)" link above.     

Oral cyclosporine in patients with active severe ulcerative colitis not responding to steroids.

Oral cyclosporine has been reported to be useful in inducing remission in patients with active severe ulcerative colitis who fail to respond to intensive steroid therapy. We present our experience of its use in six patients.     

Recurrent myopericarditis with extensive ulcerative colitis

A 26-year-old man with ulcerative colitis was independently evaluated in different emergency rooms on two occasions, separated by six years, for episodes of severe chest pain consistent with myopericarditis. Cardiac enzyme and electrocardiographic changes were accompanied by extensive colonic inflammatory changes. Treatment with corticosteroids led to resolution. While his cardiac findings were initially believed to be caused by a previously reported drug hypersensitivity to mesalamine (5-aminosalicylate), sulphasalazine was tolerated. Recurrent myopericarditis with ulcerative colitis appears to be rare, but responsive to steroids. It may occur more often than is currently appreciated and may lead to fatal arrhythmias or cardiac failure.     

Oral budesonide is as effective as oral prednisolone in active Crohn's disease

Background—The use of corticosteroids in activeCrohn's disease often becomes limited by side effects. Budesonide is apotent corticosteroid with low systemic bioavailability due to anextensive first pass liver metabolism.
Aims—To compare the efficacy and safety of twodosage regimens of budesonide and prednisolone in patients with activeCrohn's disease affecting the ileum and/or the ascending colon.
Patients and methods—One hundred and seventy eightpatients were randomised to receive budesonide controlled ileal release (CIR) capsules 9 mg once daily or 4.5 mg twice daily, or prednisolone tablets 40 mg once daily. The treatment period was 12 weeks. The primary efficacy variable was clinical remission, defined as a Crohn'sDisease Activity Index (CDAI) of 150 or less.
Results—After eight weeks of treatment, remissionoccurred in 60% of patients receiving budesonide once daily orprednisolone and in 42% of those receiving budesonide twice daily(p=0.062). The presence of glucocorticoid associated side effects wassimilar in all groups; however, moon face was more common in theprednisolone group (p=0.0005). The highest frequency of impairedadrenal function, as measured by a short ACTH test, was found in theprednisolone group (p=0.0023).
Conclusions—Budesonide CIR, administered at 9 mgonce daily or 4.5 mg twice daily, is comparable to prednisolone ininducing remission in active Crohn's disease. The single doseadministration is as promptly effective as prednisolone and representsa simpler and safer therapeutic approach, with a considerable reduction in side effects.

Keywords:adrenal function; CDAI; glucocorticoid; glucocorticoid associated side effects

     

Oral fluticasone propionate in active distal ulcerative colitis.

Fluticasone propionate is a new corticosteroid with low systemic bioavailability. This study reports the outcome of a double blind clinical trial comparing oral fluticasone propionate (5 mg four times daily) with placebo for the treatment of active distal ulcerative colitis. Sixty patients were treated for four weeks, with assessments at two and four weeks. One patient was withdrawn when she was found to have amoebiasis. Thus, results are presented for 29 patients who received placebo and 30 who received fluticasone propionate. The two groups were well matched for age, sex, length of history, and extent of disease. After four weeks of therapy the clinical, sigmoidoscopic, and histological responses were similar in the two groups. It is concluded that fluticasone propionate (5 mg four times daily) is not effective treatment for active distal ulcerative colitis.     

布地奈得和氢化可的松灌肠治疗溃疡性结肠炎的对比研究

对比观察布地奈得（ＢＵＤ）和氢化可的松（ＨＤ）灌肠治疗轻、中度远段溃疡性结肠炎的疗效及副作用;建立高效液相色谱仪检测血和结肠粘膜炎ＨＤ浓度的方法。方法随机对照单盲观察ＢＵＤ组１２例,ＨＤ组１９例ＵＣ患者。治疗２经较两组在临床症状,肠镜下,组强及学Ｗｉｌｌｉａｎ疾病活动指数几方面的变化;     

Oral budesonide therapy improves quality of life in patients with collagenous colitis

Introduction Collagenous colitis is an idiopathic microscopic colitis characterised by watery diarrhoea. The impact of collagenous colitis on quality of life has not been assessed. Our aim was to assess quality of life in patients with this condition and compare the effect of treatment with budesonide capsules or placebo on this parameter.Methods Patients with chronic diarrhoea and histologically-proven collagenous colitis were randomised to receive either budesonide controlled-release capsules (Entocort capsules, AstraZeneca, Lund, Sweden), 9 mg/day, or placebo for 6 weeks. Quality of life was measured using the validated Gastrointestinal Quality of Life Index (GIQLI) at baseline and after 6 weeks. With the GIQLI, scores range from 0 to 144, with higher scores representing better quality of life.Results Complete quality of life assessment was available in 29 patients (budesonide: n=17; placebo: n=12). At baseline, quality of life was low in patients with collagenous colitis (mean 76). After 6 weeks of treatment, the mean GIQLI score increased significantly in the budesonide group (from 67 to 92, p<0.001), but remained unchanged in the placebo group (86–88). The mean score of the dimensions symptoms (p=0.001), emotional functioning (p=0.003) and physical functioning (p=0.017) increased significantly in the budesonide group compared with the placebo group. A significantly larger proportion of patients in the budesonide group experienced improved stool consistency (p<0.01) and a significant reduction in the mean stool frequency compared with those in the placebo group (p<0.01).Conclusion Quality of life is seriously reduced in patients with collagenous colitis. Six-week treatment with oral budesonide controlled-release capsules significantly improves quality of life and clinical symptoms compared with placebo in these patients.     

Quantitative distribution of radiolabeled 5-Aminosalicylic acid enemas in patients with left-sided ulcerative colitis

Rectally administered suspensions of 5-aminosalicylic acid (5-ASA) are topically effective in treating left-sided ulcerative colitis. The extent to which the contents of these enemas are distributed to inflamed mucosal linings has not previously been determined. This study was undertaken to validate a technique for labeling 5-ASA with^99mTc and to quantitate the distribution of [^99mTc]5-ASA in eight patients with left-sided ulcerative colitis. Eight patients underwent three colonic scintigraphic exams within five days, receiving a 60-ml radiolabeled 5-ASA enema into the unprepared rectum for each study, with sequential anterior abdominal images obtained for 4 hr. Activity within the rectum, sigmoid, descending, transverse, and ascending colon was quantitated. Over 50% of the labeled enema had advanced beyond the rectum in five of eight patients and in six of eight patients by 30 min and 60 min, respectively. The distribution of [^99mTc]5-ASA was quantitatively reproducible when repeated in the same patient on different days, despite apparent visual differences. By 2 hr, the amount of the enema present within the rectum decreased significantly (P<0.05) compared to the initial distribution. The amount of enema present within the descending colon was increased significantly at 0.5 hr (P< 0.05) and at 2 hr (P< 0.01). There were no significant changes in the distribution from initial values for the sigmoid, transverse, or ascending colon at any time. In each of these cases the spread of the enema to or beyond the extent of disease was documented. In patients with left-sided ulcerative colitis, small volume [^99mTc]5-ASA enemas reliably reach the area of inflammation.Supported by a grant from Reid-Rowell, Inc.     

The clinical significance of right-sided colonic inflammation in patients with left-sided chronic ulcerative colitis

BACKGROUND: Rarely, patchy right colonic inflammation has been observed in patients with left sided chronic ulcerative colitis (CUC), but the clinical significance of this finding is unknown. Therefore, the aim of this study was to evaluate the clinical and pathologic features and natural history of CUC patients with left-sided colitis combined with patchy right colonic inflammation and to compare the clinical course to a control group of patients with isolated left-sided CUC. METHODS: Twelve patients with clinically and pathologically confirmed left-sided CUC, but also with patchy right colonic inflammation, were identified from a cohort of 352 consecutive patients with CUC who underwent colonoscopy at the Brigham and Women's Hospital between 1996 and 2000. In this cohort, 127 patients had left-sided colitis. As the first study to use controls in this setting, 35 consecutive patients with left-sided CUC, but without patchy right colonic inflammation, were selected and evaluated during the same time period. In all patients, the medical records were reviewed for a wide variety of clinical, endoscopic, and pathologic features. The mean follow-up time for the study and control groups was 105 +/- 128 and 112 +/- 80 months, respectively. RESULTS: Patients in the study group were significantly older than the control group at the time of diagnosis (47 +/- 17 years vs 35 +/- 14 years, p = 0.048), but the two groups had a similar gender distribution (25% male vs 40% male), prevalence of extraintestinal manifestations (25% vs 11%), frequency of nonsteroidal anti-inflammatory drug use (75% vs 50%), family history of colitis (27% vs 15%), current tobacco use (8% vs 3%), history of appendectomy (8% vs 0%), and overall severity of disease (33% vs 46%). None of the patients in the study group, and only one control patient, had disease progression to pancolitis. One study patient developed high-grade dysplasia in the rectum that required a colectomy. None of the study or control patients developed clinical or pathologic features of Crohn's disease. CONCLUSIONS: Rarely patients with left-sided CUC may have patchy right colonic inflammation. The clinical features and natural history of patients with left-sided CUC and patchy right colonic inflammation is similar to patients with isolated left-sided CUC.     

Granulocytapheresis in the treatment of patients with active ulcerative colitis

In recent years, considering the role of inflammatory processes and the involvement of the immune system in ulcerative colitis, granulocytapheresis, a technique for removing circulating leukocytes and preventing their migration into the intestinal mucosa, has been proposed for the treatment of acute ulcerative colitis. Initially introduced for the treatment of patients who did not respond to conventional therapy only, this new therapy may become a useful and safe method to induce clinical remission in patients with acute disease. This article will review the clinical applications and issues concerning the use of granulocytapheresis in ulcerative colitis.     

Intensive granulocyte and monocyte adsorption versus intravenous prednisolone in patients with severe ulcerative colitis: An unblinded randomised multi-centre controlled study

BACKGROUND AND AIM: Several uncontrolled studies have reported on the efficacy of adsorptive depletion of peripheral blood granulocytes and monocytes/macrophages (GM) in patients with moderate or severe ulcerative colitis. This study was to compare the efficacy and safety of intensive GMA with intensive intravenous prednisolone in patients with severe ulcerative colitis. METHODS: Seventy patients with clinical activity index 10-23 were randomly assigned to intensive GMA with the Adacolumn, at 2 sessions/week in the first 3 weeks and then 1 session/week for up to 11 sessions (n = 35) or intravenous prednisolone, 40-60 mg/day for 5-10 days (n = 35). No patient received immunomodulators within 8 weeks prior to entry. Clinical response based on intention to treat was assessed at weeks 2, 6 and 12. RESULTS: Four patients in the prednisolone group and two patients in the GMA group discontinued in week 1. At weeks 2, 6 and 12, the remission (clinical activity index < or = 4) rates (%) in the GMA group were 17.1, 54.4, 74.3, respectively. The corresponding values in the prednisolone group were 25.7, 51.4 and 48.6. Further, at week 12, 27 patients (77%) in the GMA group and 5 patients (14%) in the prednisolone group were steroid free (P = 0.0076). In the GMA group, flushing and light-headedness were observed in 5 patients versus typical steroid side effects in 29 patients of the prednisolone group. CONCLUSIONS: In this clinical response to GMA was comparable or better than prednisolone. Further, the response to GMA was slower than to intravenous prednisolone, but was more sustainable than the latter.     

A comparison of sucralfate and prednisolone enemas in the treatment of active distal ulcerative colitis

Sucralfate is well established in the treatment of upper gastrointestinal inflammation and ulceration, and preliminary evidence suggests it may be of benefit in active colitis. We have therefore undertaken a clinical trial to compare enemas of sucralfate (4 g) and prednisolone metasulphobenzoate (20 mg) in the treatment of active distal ulcerative colitis. Forty-four patients were entered into a 4-week study. Two patients were withdrawn because of non-compliance, and five were unable to complete the study: two developed constipation (both allocated to sucralfate) and three were unable to retain the enemas (two prednisolone and one sucralfate). Intention-to-treat analysis showed significant within-treatment improvement in rectal bleeding, sigmoidoscopic grade, and histologic grade in the prednisolone-treated group, and in stool frequency, rectal bleeding, and sigmoidoscopic grade in the sucralfate-treated group. Between-treatment comparisons, however, showed greater resolution of rectal bleeding and more marked improvements in histologic grade in patients treated with prednisolone metasulphobenzoate enemas. Further studies using higher doses of sucralfate would be useful.     

Acute appendicitis in inactive extensive ulcerative colitis

Appendectomy is associated with a reduced risk of developing ulcerative colitis (UC). In addition, there may be appendicular involvement in UC in patients with extensive or even left-sided disease. However, no data are available on the incidence, clinical presentation and outcome of acute appendicitis in patients previously diagnosed with UC. The impact of appendectomy in this subset of patients also remains to be determined. We describe 2 cases of acute appendicitis in the setting of inactive extensive ulcerative colitis and compare their histologic features with those of the surgical specimens of 2 further UC patients colectomized for refractory and extensive disease.     

Characteristic endoscopic findings and risk factors for cytomegalovirus-associated colitis in patients with active ulcerative colitis

AIM: To identify characteristic endoscopic findings and risk factors for cytomegalovirus(CMV)-associated colitis in patients with active ulcerative colitis(UC).METHODS: A total of 149 UC patients admitted to the Department of Gastroenterology, Nagoya University Hospital, from January 2004 to December 2013 with exacerbation of UC symptoms were enrolled in this retrospective study. All medical records, including colonoscopy results, were reviewed. CMV infection was determined by the presence of CMV antigen, CMV inclusion bodies in biopsy specimens, or positive specific immunohistochemical staining for CMV. Multivariate analysis was used to identify independent risk factors for CMV colitis.RESULTS: Multivariate analysis indicated independent associations with the extent of disease(pancolitis) anduse of > 400 mg corticosteroids for the previous 4 wk. In contrast, no association was seen with sex, age at UC diagnosis, immunomodulator use, or infliximab use. Punched-out ulceration was also significantly associated with CMV infection in patients with active UC(odds ratio = 12.672, 95%CI: 4.210-38.143).CONCLUSION: Identification of a total corticosteroid dose > 400 mg for 4 wk, extensive colitis and a specific endoscopic finding of punched-out ulcer might facilitate the more rapid diagnosis and timely initiation of antiviral therapy for CMV-associated colitis in patients with active UC.     

VSL#3 probiotic-mixture induces remission in patients with active ulcerative colitis

BACKGROUND AND AIMS: Intestinal bacteria have been implicated in the initiation and perpetuation of IBD; in contrast, "probiotic bacteria" have properties possibly effective in treating and preventing relapse of IBD. We evaluated the safety and efficacy of VSL#3 and the components, and the composition of the biopsy-associated microbiota in patients with active mild to moderate ulcerative colitis (UC). METHODS: Thirty-four ambulatory patients with active UC received open label VSL#3, 3,600 billion bacteria daily in two divided doses for 6 wk. The presence of biopsy-associated bacteria was detected using a nucleic acid-based method and the presence of VSL#3 species confirmed by DNA sequencing of 16S rRNA. RESULTS: Thirty-two patients completed 6 wk of VSL#3 treatment and 2 patients did not have the final endoscopic assessment. Intent to treat analysis demonstrated remission (UCDAI < or = 2) in 53% (n = 18); response (decrease in UCDAI > or = 3, but final score > or =3) in 24% (n = 8); no response in 9% (n = 3); worsening in 9% (n = 3); and failure to complete the final sigmoidoscopy assessment in 5% (n = 2). There were no biochemical or clinical adverse events related to VSL#3. Two of the components of VSL#3 were detected by PCR/DGGE in biopsies collected from 3 patients in remission. CONCLUSION: Treatment of patients with mild to moderate UC, not responding to conventional therapy, with VSL#3 resulted in a combined induction of remission/response rate of 77% with no adverse events. At least some of the bacterial species incorporated in the probiotic product reached the target site in amounts that could be detected.