Infliximab safety profile and long‐term applicability in inflammatory bowel disease: 9‐year experience in clinical practice

Aliment Pharmacol Ther 31 , 553–560

Summary

Background Most available data on infliximab therapy come from large, short‐term, pivotal RCTs and concerns about long‐term safety profile still remain. Aim To evaluate the long‐term safety profile of infliximab in inflammatory bowel disease (IBD) in a clinical practice setting. Methods Since 1999, all IBD patients treated with infliximab were registered and clinical outcomes prospectively recorded up to March 2008, loss of follow‐up or patient’s death. Infliximab regimens and preventive measures were in accordance with the prevalent guidelines or with the manufacturer’s recommendations. Results One hundred fifty‐two patients were included (121 Crohn’s disease, 24 ulcerative colitis, 7 indeterminate colitis), with a median of 5 infliximab infusions (IQR 3–8) and 87% of patients received at least three infusions. Seventy‐nine per cent of them received concomitant immunomodulators and 70% were pre‐medicated with hydrocortisone from the first infusion. After a median follow‐up of 142 weeks, 13% presented infusion reactions, 13% viral or bacterial infections and two patients developed neoplasia. The mortality rate was 2.6% (four patients). Conclusions Infliximab therapy is safe when the recommended preventive measures are implemented, with a rate of serious adverse events less than 10%. No new safety signals were found.     

Meta‐analysis: targeting the intestinal microbiota in prophylaxis for post‐operative Crohn’s disease

Aliment Pharmacol Ther 31 , 802–809

Summary

Background Enteric bacteria play an important early role in the pathogenesis of Crohn’s disease. Aim To perform a meta‐analysis of trials testing antibiotics or probiotics for prevention of post‐operative recurrence of Crohn’s disease. Methods Review of all randomized controlled trials comparing antibiotics or probiotics with placebo in prevention of endoscopic or clinical recurrence of Crohn’s disease after surgical resection. Fixed‐effect meta‐analysis was performed with dichotomous data summarized using relative risk with 95% confidence intervals, where appropriate. Results Seven studies were identified as suitable for inclusion (two comparing antibiotics with placebo, five comparing probiotics with placebo). The use of nitroimidazole antibiotics (metronidazole, ornidazole) reduced the risk of clinical (RR 0.23; 95% CI 0.09–0.57, NNT = 4) and endoscopic (RR 0.44; 95% CI 0.26–0.74, NNT = 4) recurrence relative to placebo. However, these agents were associated with higher risk of adverse events (RR 2.39, 95% CI 1.5–3.7) and patient withdrawal. Probiotic administration was not associated with any significant difference in risk of recurrence compared with placebo. Conclusions Nitroimidazole antibiotics are effective in the prevention of post‐operative Crohn’s disease recurrence, but their side‐effects limit acceptability. Probiotics have failed to show efficacy for post‐operative prophylaxis, but may merit further study.     

Treatment of ulcerative colitis with adalimumab or infliximab: long‐term follow‐up of a single‐centre cohort

Aliment Pharmacol Ther 2010; 32: 522–528

Summary

Background Randomized, controlled trials have demonstrated that anti‐TNF agents are efficacious in inducing remission in cases of Crohn’s disease and ulcerative colitis. However, response rates for anti‐TNF agents in ‘real life’ clinical practice are less well‐defined. Aims To examine the response rates and long‐term outcomes of infliximab and adalimumab treatment for out‐patients with ulcerative colitis and to study the variables associated with response rates. Methods In a prospective study, a single‐centre out‐patient cohort was treated and followed up according to a structured protocol of clinical care. Response to treatment was assessed using a physician’s global assessment that focused on normalization of bowel frequency, absence of blood with defecation and tapering of corticosteroids to zero. Results Fifty‐three ulcerative colitis patients were included in the study. Responses to induction therapy were 96.4% (27/28) for infliximab and 80% (20/25) for adalimumab (P = 0.0889). Responses to maintenance therapy were similar: infliximab 77.8% (14/18) and adalimumab 70.0% (14/20) (P = 0.7190). Multivariate analyses of the induction and maintenance responses did not reveal confounding elements. No new safety signals were identified. Conclusions This long‐term follow‐up of a single‐centre cohort of ulcerative colitis patients demonstrates that ‘real‐life’ out‐patient treatment with infliximab and adalimumab is effective in induction and maintenance of response.     

Pre‐operative management is associated with low rate of post‐operative morbidity in penetrating Crohn’s disease

Aliment Pharmacol Ther 2010; 32: 459–465

Summary

Background Ileocaecal resection for penetrating Crohn’s disease is still challenging with a high rate of post‐operative morbidity and faecal diversion. Aim To report retrospectively the results of pre‐operative management for penetrating Crohn’s disease focusing on the rate of post‐operative major morbidities and need for faecal diversion. Methods Between 1997 and 2007, 78 patients with penetrating Crohn’s disease underwent a first ileocaecal resection after a pre‐operative management consisting in bowel rest, nutritional therapy, intravenous antibiotics, weaning off steroids and immunosuppressors, and drainage of abscesses when appropriate. Results Resection was performed for terminal ileitis associated with (n = 41), abscesses (n = 37) or both (n = 5). A pre‐operative nutritional therapy was performed in 50 patients (68%) for 23 days (range, 7–69 days) along with a weaning off steroids and immunosuppressors. A diverting stoma was performed for six patients (7.7%). There was no post‐operative death. Post‐operative complications were classified as minor in 10 patients (12.8%), and major in four patients (5%). Overall, the post‐operative course was uneventful in 58 patients (74%). Conclusion Pre‐operative management for penetrating Crohn’s disease allowed ileocaecal resection with low rates of post‐operative morbidity and faecal diversion.     

The impact of infliximab infusion reactions on long-term outcomes in patients with Crohn's disease

Background Little is known about long‐term outcomes in patients who experience infusion reactions while receiving infliximab. Aim To investigate long‐term outcomes in patients who experience infusion reactions while receiving infliximab. Methods Retrospective electronic chart review of long‐term clinical outcomes. Results Clinical data on 287 patients who received infliximab infusions for Crohn’s disease were reviewed, of whom 51 developed at least one infusion reaction (18%). Ileo‐colonic disease (OR 2.2, 95% CI 1.1–4.4) and episodic infliximab (OR 2.4, 95% CI 1.2–4.7) were associated with a higher risk of infusion reactions in univariate analysis, but concomitant azathioprine/mercaptopurine therapy at the initiation of infliximab was associated with a reduced risk (OR 0.4, 95% CI 0.2–0.8). Only the effect of concomitant immunomodulators persisted on multivariate analysis. Patients who experienced infusion reactions were less likely to be in remission at 1 year (OR 0.6, 95% CI 0.3–1.2), 2 years (OR 0.4, 95% CI 0.2–0.8, P = 0.01), or 5 years (OR 0.4, 95% CI 0.1–1.3) and more likely to require surgery (OR 2.2, 95% CI 1.1–4.1, P = 0.01) than those who did not experience such reactions. Conclusions Patients who experienced infusion reactions to infliximab had a high rate of discontinuation of therapy in this cohort. Concomitant immunomodulators and maintenance therapy reduced the risk of infusion reactions.     

Adalimumab induction and maintenance therapy for patients with ulcerative colitis previously treated with infliximab

Aliment Pharmacol Ther 2011; 33: 340–348

Summary

Background The long‐term efficacy of adalimumab in patients with ulcerative colitis is not well known. Aim To evaluate the short‐ and long‐term outcomes of adalimumab in ulcerative colitis patients previously treated with infliximab. Methods Patients with active ulcerative colitis were treated with adalimumab after failure of other therapies including infliximab. Short‐term clinical response and remission were assessed at weeks 4 and 12. The proportion of patients who continued on adalimumab and the proportion of patients who remained colectomy free were assessed over the long term. Results Clinical response at weeks 4 and 12 was achieved in 16 (53%) and 18 (60%) patients, respectively, and clinical remission was obtained in 3 (10%) and 8 (27%) patients, respectively. After a mean 48 weeks’ follow‐up, 15 patients (50%) continued on adalimumab. Six patients (20%) required colectomy. All patients who achieved clinical response at week 12 were colectomy free at long term. Conclusions Adalimumab was well tolerated and induced durable clinical response in many patients with otherwise medically refractory ulcerative colitis. Patients achieving clinical response at week 12 avoided colectomy over the long term.     

Effect of pharmaceutical pre‐assessment on post‐operative interventions

□ The study determined the extent of post‐operative interventions required for patients admitted for elective hip or knee arthroplasty □ In Phase 1, patients were pre‐assessed by nurses at admission, according to existing practice; in Phase 2, patients received pharmacist‐led pre‐assessment □ There were 131 interventions (2.05 per patient) in Phase 1 compared with 40 (0.68 per patient) in Phase 2, a reduction of approximately 70 per cent □ This study demonstrates that pharmaceutical pre‐assessment substantially reduces the number of interventions made during patients' post‐operative stay.     

Systematic review: Infliximab therapy in ulcerative colitis

AIM: To perform a systematic review and meta-analysis on the efficacy and tolerance of infliximab in ulcerative colitis. METHODS: Selection of studies: evaluating efficacy of infliximab in ulcerative colitis. For the meta-analysis, randomized clinical trials comparing infliximab vs. placebo/steroids. Search strategy: electronic and manual. Study quality: independently assessed by two reviewers. Data synthesis: meta-analysis combining the odds ratios (OR). RESULTS: Thirty-four studies (896 patients) evaluated infliximab therapy in UC, with heterogeneous results. Mean short-term (2.3 weeks) response and remission with infliximab was 68% (95% CI 65-71%) and 40% (36-44%). Mean long-term (8.9 months) response and remission was 53% (49-56%) and 39% (35-42%). Five randomized double-blind studies compared infliximab with placebo, the meta-analysis showing an advantage (P < 0.001) of infliximab in all endpoints (short-/long-term response/remission): ORs from 2.7 to 4.6, and number-needed-to-treat (NNT) from 3 to 5. Similar infliximab response was calculated independently of the indication (steroid-refractory/non-steroid-refractory) or the dose (5/10 mg/kg). Adverse effects were reported in 83% and 75% of the infliximab and placebo-treated patients (OR = 1.52; 95% CI 1.03-2.24; number-needed-to-harm (NNH) was 14). CONCLUSION: Infliximab is more effective than placebo, with an NNT from 3 to 5, for the treatment of moderate-to-severe UC, achieving clinical remission in 40% of the patients at approximately 9 months of follow-up. Further studies are necessary to confirm the long-term efficacy of infliximab in ulcerative colitis.     

Tranexamic Acid in Total Knee Arthroplasty: Mixed Treatment Comparisons and Recursive Cumulative Meta‐Analysis of Randomized,Controlled Trials and Cohort Studies

Tranexamic acid (TXA) has been shown to be effective in patients with total knee arthroplasty (TKA) in clinical studies with no consensus with regard to the most appropriate route of administration. We conducted a network meta‐analysis to compare the evidence available on efficacy and safety of TXA in TKA. Electronic databases were searched for randomized, clinical trials and cohort studies that evaluated TXA in TKA. Publication bias, risk of bias and inconsistencies were assessed. Direct and indirect comparisons were carried out for blood transfusion rate and incidence of thrombotic complications. Sensitivity analyses and grading of evidence were performed for key comparisons. A cumulative meta‐analysis was conducted for comparisons that had a minimum of 10 included studies. A total of 19 studies with 8916 participants were pooled for this network meta‐analysis. No inconsistencies and publication bias were observed. Low risk of bias was observed for the majority of the included studies. When compared to placebo, the pooled estimates for mixed treatment analyses favoured (in the order of higher ranking) the combined pre‐operative oral and topical TXA, intra‐operative intravenous TXA with topical TXA, pre‐operative intravenous TXA, intra‐operative and post‐operative intravenous TXA, intra‐operative intravenous bolus and topical TXA. Additionally, combined intravenous and topical TXA performed better than topical TXA alone. No significant changes were observed in the sensitivity analyses. No significant differences were observed in the risk of thrombotic complications between the interventions. TXA is efficacious and safe in patients with TKA. The combined topical and intra‐operative intravenous TXA may perform better.     

Infliximab in severe ulcerative colitis: short-term results of different infusion regimens and long-term follow-up

BACKGROUND: Severe ulcerative colitis is a life-threatening disorder, despite i.v. glucocorticoids treatment. Infliximab has been proposed as a safe rescue therapy. AIM: To evaluate short- and long-term effectiveness and safety of infliximab in severe refractory ulcerative colitis. METHODS: Eighty-three patients with severe ulcerative colitis (i.v. glucocorticoids treatment-refractory) were treated with infliximab in 10 Italian Gastroenterology Units. Patients underwent one or more infusions according to the choice of treating physicians. Short-term outcome was colectomy/death 2 months after the first infusion. Long-term outcome was survival free from colectomy. Safety data were recorded. RESULTS: Twelve patients (15%) underwent colectomy within 2 months. One died of Legionella pneumophila infection 12 days after infliximab. Early colectomy rates were higher in patients receiving one infusion (9/26), compared with those receiving two/more infusions (3/57, P = 0.001, OR = 9.53). Seventy patients who survived colectomy and did not experience any fatal complications were followed-up for a median time of 23 months; 58 patients avoided colectomy during the follow-up. Forty-two patients were maintained on immunosuppressive drugs. No clinical features were associated with outcomes. CONCLUSIONS: Infliximab is an effective and relatively safe therapy to avoid colectomy and maintain long-term remission for patients with severe refractory ulcerative colitis. In the short term, two or more infusions seem to be more effective than one single infusion.     

Clinical trial: colectomy after rescue therapy in ulcerative colitis - 3-year follow-up of the Swedish-Danish controlled infliximab study

Aliment Pharmacol Ther 2010; 32: 984–989

Summary

Background The long‐term efficacy of infliximab as rescue therapy in steroid‐refractory ulcerative colitis is not well described. Aim To examine the long‐term efficacy of infliximab as a rescue therapy through a 3‐year follow‐up of a previous placebo‐controlled trial of infliximab in acute steroid‐refractory ulcerative colitis. Method In the original study, 45 patients were randomized to a single infusion of infliximab 5 mg/kg or placebo, and at 3 months, 7/24 patients given infliximab were operated vs. 14/21 patients given placebo. Three years or later, patients were asked to participate in a clinical follow‐up. Results Another seven patients underwent colectomy during follow‐up: five in the infliximab group and two in the placebo group. After 3 years, a total of 12/24 (50%) patients given infliximab and 16/21 (76%) given placebo (P = 0.012) had a colectomy. None of eight patients in endoscopic remission at 3 months later had a colectomy compared with 7/14 (50%) patients who were not in remission (P = 0.02). There was no mortality. Conclusion The benefit of rescue therapy with infliximab in steroid‐refractory acute ulcerative colitis remained after 3 years. The main advantage of infliximab treatment occurred during the first 3 months, whereas subsequent colectomy rates were similar in the two groups. Mucosal healing at 3 months influenced later risk of colectomy.     

Meta‐analysis of the role of high‐dose statins administered prior to percutaneous coronary intervention in reducing major adverse cardiac events in patients with coronary artery disease

1. There is considerable evidence regarding the efficacy of statins for the primary and secondary prevention of coronary artery disease (CAD). However, due to lack of sufficient evidence, there is still doubt whether high‐dose statin therapy prior to percutaneous coronary intervention (PCI) is beneficial. In the present study, we performed a meta‐analysis to evaluate the effect of preoperative high‐dose statin therapy on the incidence of major adverse cardiac events (MACE) after successful PCI. 2. Trials were retrieved through Medline (1980–2009) and the reference files limited to English‐language articles. Data were abstracted using a standardized protocol and a meta‐analysis was performed. 3. Five studies of a total 1789 patients with CAD qualified for analysis. Administration of high‐dose statins in CAD patients before PCI was associated with a significant reduction in MACE 30 days after the procedure. The incidence of MACE in the high‐dose statin group (6.98%) was significantly lower than that in the placebo group (14.77%), with an odds ratio (OR) of 0.43 (95% confidence interval (CI) 0.31–0.59; P < 0.00001). The incidence of post‐PCI increases in creatine kinase MB in the high‐dose statin and placebo groups was 9.20%vs 18.83%, respectively (OR 0.43; 95% CI 0.33–0.58; P < 0.00001), whereas the incidence of increases in troponin I was 30.13%vs 44.53%, respectively (OR 0.53; 95% CI 0.43–0.67; P < 0.00001), respectively. 4. In conclusion, high‐dose statin therapy before PCI provides a significant benefit over placebo in preventing post‐PCI MACE. Findings from the present analysis strongly support a strategy of routine loading of high‐dose statins before interventional therapy.     

Infliximab as rescue medication for patients with severe ulcerative/indeterminate colitis refractory to tacrolimus

Aliment Pharmacol Ther 31 , 1036–1041

Summary

Background The calcineurin inhibitor tacrolimus and the anti‐TNF‐antibody infliximab are established options in steroid‐refractory ulcerative colitis (UC). Aim To evaluate the efficacy of infliximab‐salvage therapy in patients with refractory UC failing to respond to tacrolimus. Methods Twenty‐four patients were enrolled in this evaluation. Reasons for tacrolimus therapy were steroid‐refractory disease in 19 patients and steroid‐dependency in five patients. All patients receiving infliximab had tacrolimus‐refractory active disease (Lichtiger score >10) and were treated with 5 mg/kg at weeks 0, 2 and 6 and every 8 weeks thereafter, if tolerated. Results Six of 24 patients (25%) achieved remission following infliximab infusion and four of 24 (17%) had an initial response only, but underwent proctocolectomy later because of loss of response (3) or development of a delayed hypersensitivity reaction (1). Fourteen patients (58%) completely failed to respond with 10 undergoing colectomy. Eight patients experienced side effects under infliximab, including two infectious complications (herpes zoster and herpes pneumonia). Conclusions Infliximab offers a therapeutic option as rescue therapy in about a quarter of patients with active UC after failing to respond to tacrolimus. This benefit has to be weighed against the risks of infectious complications.     

Meta‐analysis: reduction in hepatic events following interferon‐alfa therapy of chronic hepatitis B

Aliment Pharmacol Ther 2010; 32: 1059–1068

Summary

Background The long‐term benefit of interferon‐alfa (IFN‐α) treatment in preventing various hepatic complications is not certain. Aim To study the effects of IFN‐α on reducing the risk of developing overall hepatic events (hepatocellular carcinoma, cirrhotic complications and liver‐related mortality) in chronic hepatitis B patients. Methods Randomized controlled trials, case–control studies and cohort studies were retrieved from electronic databases and conference abstracts. Relative risks (RRs) of different hepatic complications among patients treated by IFN‐α vs. no treatment or placebo were studied. Results Eleven studies were identified totalling 975 patients treated by IFN‐α vs. 1147 untreated controls for analysis. Patients were treated by IFN‐α for 1–24 months with a post‐treatment follow‐up of 1–13 years. Treatment by IFN‐α reduced the risk of overall hepatic events (RR 0.55, 95% confident interval or CI 0.43–0.70, P < 0.001) and cirrhotic complications (RR 0.46, 95% CI 0.32–0.67, P < 0.001) by 45% and 54% respectively. Patients who responded to IFN‐α had more profound reduction in overall hepatic events (RR 0.20, 95% CI 0.05–0.87, P = 0.03) and cirrhotic complications (RR 0.19, 95% CI 0.09–0.38, P < 0.001) vs. the untreated controls. Conclusion Interferon‐alfa treatment reduces the risk of hepatic events particularly among responders to treatment.     

Long-term outcome of adalimumab therapy for ulcerative colitis with intolerance or lost response to infliximab: a single-centre experience

Background Adalimumab may be effective in inducing remission in patients with mild‐to‐moderate ulcerative colitis who had secondary failure to infliximab. Aim To evaluate long‐term efficacy and safety of adalimumab in patients with ulcerative colitis who previously responded to infliximab, and then lost response or became intolerant. Methods We report our single‐centre experience in 13 patients. The patients received a loading dose of 160 mg of adalimumab subcutaneously in week 0, followed by 80 mg at week 2 and then 40 mg every other week starting at week 4. The primary efficacy measure was the proportion of patients on adalimumab therapy during the study. Results Median duration of follow‐up was 42 weeks (range, 10–100). The mean number of adalimumab infusions was 21 (range, 5–50). The probability of maintaining adalimumab was 92.3%, 84.6%, 60.6% and 32.5% at 1, 3, 6 and 23 months respectively. Six of 13 patients (46.2%) underwent colectomy during the study. No serious toxicities occurred in the study. Conclusion Adalimumab is well‐tolerated and may be effective in maintaining clinical remission in a subgroup of patients with ulcerative colitis and lost response or intolerance to infliximab, potentially avoiding colectomy in about half of the patients.     

Meta‐analysis: proton pump inhibitor use and the risk of community‐acquired pneumonia

Aliment Pharmacol Ther 31 , 1165–1177

Summary

Background Observational studies examining the association between proton pump inhibitor (PPI) use and risk of community‐acquired pneumonia are conflicting. Aim To assess systematically the association between risk of community‐acquired pneumonia and PPI use in adults. Methods We searched MEDLINE, EMBASE and CINAHL databases between 1988 and January 2010. Two reviewers independently selected studies based on eligibility criteria and extracted data. Included studies evaluated adults (≥18 years) who took PPIs as an out‐patient. The primary outcome was community‐acquired pneumonia. Only observational studies with a comparison arm were included. Results Over 2600 citations were reviewed. Six studies were included. All were nested case‐control studies. Meta‐analysis found an increased risk of community‐acquired pneumonia associated with PPI use [OR 1.36 (95% CI 1.12–1.65)]; significant heterogeneity remained (I² 92%, P < 0.001). In exploratory subgroup analysis, short duration of use was associated with an increased odds of community‐acquired pneumonia [OR 1.92 (95% CI 1.40–2.63), I² 75%, P = 0.003], whereas chronic use was not [OR 1.11 (95% CI 0.90–1.38), I² 91%, P < 0.001], a significant interaction (P < 0.005). Conclusions Heterogeneity precluded interpretation of the summary statistic. Exploratory analysis revealed that duration of PPI use may impact the risk of community‐acquired pneumonia, a finding that should be explored in future studies.     

Meta-analysis: The utility and safety of heparin in the treatment of active ulcerative colitis

BACKGROUND: The use of heparin for the treatment of ulcerative colitis has been evaluated in several open and controlled trials, with varying outcomes. AIM: To evaluate the efficacy and safety of heparin as supplemental therapy compared with conventional therapy in patients with ulcerative colitis. METHODS: All randomized trials comparing heparin supplementation to conventional therapy were included from electronic databases. Statistical analysis was performed with review manager 4.2.8 (The Cochrane Collaboration, Oxford, UK). Sub-analysis and sensitivity analysis were also performed. RESULTS: Eight randomized-controlled trials, investigating a total of 454 participants, met the inclusion criteria. The odds ratio (OR) for the efficacy of heparin supplementation vs. conventional therapy was 0.78 (95% CI = 0.50-1.21). Few serious adverse events were observed. The OR for the efficacy of unfractionated heparin and low-molecular-weight heparin vs. conventional therapy was 0.26 (95% CI = 0.07-0.93) and 0.92 (95% CI = 0.57-1.47), respectively. The OR for the efficacy of heparin vs. conventional therapy with placebo was 0.87 (95% CI = 0.53-1.44). CONCLUSIONS: Our meta-analysis suggests that administration of heparin in patients with ulcerative colitis is safe, but no additive benefit over conventional therapy is indicated.     

Review article: the optimal medical management of acute severe ulcerative colitis

Aliment Pharmacol Ther 2010; 32: 615–627

Summary

Background Management of acute severe ulcerative colitis (UC) is a clinical challenge, with a mortality rate of approximately 1–2%. The traditional management with intravenous corticosteroids has been modified by introduction of ciclosporin and more recently, infliximab. Aim To provide a detailed and comprehensive review of the medical management of acute severe UC. Methods PubMed and recent conference abstracts were searched for articles relating to treatment of acute severe UC. Results Two‐thirds of patients respond to intravenous steroids in the short term. In those who fail steroids, low‐dose intravenous ciclosporin at 2 mg/kg/day is effective. Approximately 75% and 50% of patients treated with ciclosporin avoid colectomy in the short and long‐terms, respectively. Long‐term outcome of ciclosporin therapy is improved by introduction of azathioprine on discharge from hospital, together with oral ciclosporin as a bridging therapy. Controlled data show that infliximab is effective as rescue therapy for acute severe UC and the effect appears to be durable, although longer‐term follow‐up data are needed. Conclusions Both ciclosporin and infliximab have demonstrated efficacy as rescue medical therapies in patients with acute severe UC, but surgery needs to be considered if there is failure to improve or clinical deterioration.     

Predictive factors of bleeding related to post‐banding ulcer following endoscopic variceal ligation in cirrhotic patients: a case‐control study

Aliment Pharmacol Ther 2010; 32: 225–232

Summary

Background Life‐threatening bleeding caused by early spontaneous slippage of rubber bands has been described after variceal ligation in cirrhotic patients. Aim To determine the predictive factors of this complication in cirrhotic patients. Methods Among 605 patients, 21 patients (mean age 56.6 ± 13.5 years) developed 23 spontaneous band slippages with bleeding on post banding ulcer, as confirmed by endoscopy. Cirrhosis was alcoholic in 13 patients (62%), post viral hepatitis in three (14%) and from other causes in five (24%). A case‐control study was performed comparing 17 from these patients who presented the complication after a first ligation with 84 of the 584 controls who underwent first endoscopic variceal ligation without bleeding complication. Results Bleeding occurred 13.5 days ± 7.3 (2–29) following ligation. Eleven patients died following the bleeding complication (52%). Using a multivariate analysis, previous upper variceal digestive bleeding [OR 12.07, 95%CI (2.3–63.43)], peptic oesophagitis [OR 8.9, 95%CI (1.65–47.8)], high platelet ratio index (APRI) score [OR 1.54, 95%CI (1.11–2.16)] and low prothrombin index [OR 0.54, 95% CI (0.31–0.94)] were independent predictive factors of bleeding. Conclusions Bleeding related to post‐banding ulcer is a rare, but severe complication. The proposed predictive factors should be looked for and minimized before variceal ligation.     

Review article: the management of steroid dependency in ulcerative colitis

BACKGROUND: Approximately 20% of patients with ulcerative colitis have a chronic active disease often requiring several courses of systemic steroids in order to achieve remission, but followed by relapse of symptoms during steroid tapering or soon after their discontinuation. Although short term control of symptoms can be achieved with steroid treatment, this pattern of drug response, known as steroid-dependency, leads to important complications of the treatment, while a significant proportion of patients requires colectomy. AIM: To review the studies currently available specifically evaluating the management of steroid-dependent ulcerative colitis. RESULTS: The clinical and biological mechanisms of steroid-dependency are not well understood compared with those determining steroid-refractoriness. Very few evidence-based data are available concerning the management of patients with steroid-dependent ulcerative colitis. The therapeutic role of aminosalicylates, thiopurines, methotrexate, infliximab, leukocyte apheresis and other drugs in the treatment of steroid-dependent ulcerative colitis are evaluated. CONCLUSIONS: Outcomes of studies in steroid-refractory patients may not be applicable to steroid-dependency. Trials are needed to define the correct approaches and new strategies to ameliorate the therapy of steroid-dependent ulcerative colitis.