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Biomedical subjects

W J Sandborn

Publications and source records attributed to W J Sandborn.

At least 19 recordsLinked to original sources
PubMed2007

Review article: biological activity markers in inflammatory bowel disease.

BACKGROUND: Traditionally, inflammatory bowel disease activity is assessed by clinical activity indices that measure clinical symptoms and endoscopic indices that measure endoscopic inflammation. Biological markers are a non-invasive way of objectively measuring inflammation and can play an adjunctive or primary role in the assessment of disease activity. AIM: To review the data on biological markers for assessment of disease activity and prediction of relapse in inflammatory bowel disease. METHODS: To collect relevant articles, a PubMed search was performed from 1980 to 2006 using following search terms in combination: inflammatory bowel disease, biomarkers, inflammation, disease activity, relapse, acute phase reactants cytokines, interleukins, adhesion molecules, integrins, calprotectin and lactoferrin. RESULTS: Biological activity markers can be classified into serological, faecal and miscellaneous categories. Acute phase reactants levels correlate with disease activity and some can be used to help predict relapse. Cytokines and adhesion molecules are elevated in active disease inconsistently. Faecal markers are useful in assessment of disease activity and relapse. CONCLUSIONS: Acute phase reactants and faecal markers are useful to assess the disease activity in clinical practice. More data are required on cytokines and adhesion molecules. C-reactive protein, erythrocyte sedimentation rate, interleukins and faecal markers may be useful in predicting a relapse.

Biomarkers↗
PubMed2006

Quantitative measurement and visual assessment of ileal Crohn's disease activity by computed tomography enterography: correlation with endoscopic severity and C reactive protein.

BACKGROUND: Few studies have correlated computed tomography (CT) enterography findings with endoscopic severity and C reactive protein (CRP) concentrations. AIM: To examine whether small bowel inflammation at CT enterography correlates with endoscopic severity and CRP in patients with Crohn's disease (CD). METHODS: CT enterography datasets from 143 CD patients undergoing ileoscopy were examined for three different CT parameters: CT bowel enhancement, as defined by the ratio of terminal ileal versus control ileal loop attenuation; vascular enlargement of the vasa recta ("the comb sign"); and mesenteric fat density. Correlations between CT scan parameters, endoscopy, and histology severity scores, and CRP were assessed using Spearman's rank correlation and logistic regression. RESULTS: Endoscopic score was significantly correlated with CT bowel enhancement, comb sign, and fat density (Spearman correlation coefficients 0.33-0.39; p<0.001). Correlations with histological inflammation were strongest for bowel enhancement (r = 0.34-0.38; p<0.001). CRP was elevated in patients with increased fat density versus those with increased bowel enhancement only (median 0.96 v 0.23, p = 0.002). CRP did not differ significantly between patients without evidence of active Crohn's and those with bowel enhancement and endoscopic inflammation not involving the perienteric tissues by CT (median 0.24 v 0.36; p = 0.38). CONCLUSION: Quantitative measures of bowel enhancement at CT enterography correlate with endoscopic and histological severity. CRP correlates with radiological findings of perienteric inflammation (increased fat density), but not of inflammation limited to the small bowel wall, underscoring the potential role of perienteric inflammation in CRP response in CD.

Adolescent↗
PubMed2006

Systematic review: the management of pouchitis.

Pouchitis is the most common complication following proctocolectomy and ileal pouch-anal anastomosis in patients with ulcerative colitis. We aim at discussing relevant information on epidemiology, clinical features, risk factors, diagnostic testing, differential diagnosis and treatment of this idiopathic inflammatory condition. A computerized search of PubMed was performed with the search term 'pouchitis', limited to English papers on humans. This strategy identified 514 references. Relevant articles were selected from this list. In addition, the reference list for each of the selected articles was reviewed to identify any additional references. Pouchitis occurs in up to 60% of patients after ileal pouch-anal anastomosis for ulcerative colitis, and has characteristic clinical, endoscopic and histological features. The most important test for diagnosis is pouch endoscopy with biopsy. Antibiotics remain the mainstay of treatment, and other options are discussed for those patients who are refractory to antibiotic therapy.

Anti-Bacterial Agents↗
PubMed2006

Daclizumab, a humanised monoclonal antibody to the interleukin 2 receptor (CD25), for the treatment of moderately to severely active ulcerative colitis: a randomised, double blind, placebo controlled, dose ranging trial.

BACKGROUND: An uncontrolled pilot study demonstrated that daclizumab, a humanised monoclonal antibody to the interleukin 2 receptor (CD25), might be effective for the treatment of active ulcerative colitis. METHODS: A randomised, double blind, placebo controlled trial was conducted to evaluate the efficacy of daclizumab induction therapy in patients with active ulcerative colitis. A total of 159 patients with moderate ulcerative colitis were randomised to receive induction therapy with daclizumab 1 mg/kg intravenously at weeks 0 and 4, or 2 mg/kg intravenously at weeks 0, 2, 4, and 6, or placebo. The primary end point was induction of remission at week 8. Remission was defined as a Mayo score of 0 on both endoscopy and rectal bleeding components and a score of 0 or 1 on stool frequency and physician's global assessment components. Response was defined as a decrease from baseline in the Mayo score of at least 3 points. RESULTS: Two per cent of patients receiving daclizumab 1 mg/kg (p = 0.11 v placebo) and 7% of patients receiving 2 mg/kg (p = 0.73) were in remission at week 8, compared with 10% of those who received placebo. Response occurred at week 8 in 25% of patients receiving daclizumab 1 mg/kg (p = 0.04) and in 33% of patients receiving 2 mg/kg (p = 0.30) versus 44% of those receiving placebo. Daclizumab was well tolerated. The most frequently reported adverse events in daclizumab treated patients compared with placebo treated patients were nasopharyngitis (14.6%) and pyrexia (10.7%). CONCLUSION: Patients with moderate ulcerative colitis who are treated with daclizumab are not more likely to be in remission or response at eight weeks than patients treated with placebo.

Adolescent↗
PubMed2006

CDP571, a humanized monoclonal antibody to tumour necrosis factor-alpha, for steroid-dependent Crohn's disease: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: More than 50% of patients with Crohn's disease become either steroid resistant or dependent. Accordingly, development of new treatments for steroid-dependent Crohn's disease is a research priority. AIM: To evaluate CDP571, a humanized antibody to tumour necrosis factor-alpha, for the treatment of steroid-dependent Crohn's disease. METHODS: Patients with steroid-dependent Crohn's disease (n = 271) were enrolled in a 36-week, double-blind, placebo-controlled trial. Steroid dependence was defined as use of prednisolone or prednisone (15-40 mg/day) or budesonide (9 mg/day) for > or =8 weeks, a previous failed attempt to decrease or discontinue steroids within 8 weeks of screening, and a Crohn's Disease Activity Index score of < or =150 points. Patients were randomized to receive intravenous CDP571 10 mg/kg or placebo 8-weekly through to week 32. Steroids were then tapered using a defined schedule. The primary efficacy endpoint was the percentage of patients with steroid sparing, defined as discontinuation of steroid therapy without a disease flare (Crohn's Disease Activity Index score > or =220 points) at week 36. RESULTS: Steroid sparing occurred in 53 of 181 (29.3%) CDP571 patients and 33 of 90 (36.7%) placebo patients (P = 0.24). Adverse events occurred at similar frequencies in both treatment groups. CONCLUSIONS: CDP571 was ineffective for sparing steroids in patients with steroid-dependent Crohn's disease. CDP571 was well tolerated.

Adult↗
PubMed2006

Survival and cause specific mortality in patients with inflammatory bowel disease: a long term outcome study in Olmsted County, Minnesota, 1940-2004.

BACKGROUND AND AIMS: We followed a population based cohort of patients with inflammatory bowel disease (IBD) from Olmsted County, Minnesota, in order to analyse long term survival and cause specific mortality. MATERIAL AND METHODS: A total of 692 patients were followed for a median of 14 years. Standardised mortality ratios (SMRs, observed/expected deaths) were calculated for specific causes of death. Cox proportional hazards regression was used to determine if clinical variables were independently associated with mortality. RESULTS: Fifty six of 314 Crohn's disease patients died compared with 46.0 expected (SMR 1.2 (95% confidence interval (CI) 0.9-1.6)), and 62 of 378 ulcerative colitis (UC) patients died compared with 79.2 expected (SMR 0.8 (95% CI 0.6-1.0)). Eighteen patients with Crohn's disease (32%) died from disease related complications, and 12 patients (19%) died from causes related to UC. In Crohn's disease, an increased risk of dying from non-malignant gastrointestinal causes (SMR 6.4 (95% CI 3.2-11.5)), gastrointestinal malignancies (SMR 4.7 (95% CI 1.7-10.2)), and chronic obstructive pulmonary disease (COPD) (SMR 3.5 (95% CI 1.3-7.5)) was observed. In UC, cardiovascular death was reduced (SMR 0.6 (95% CI 0.4-0.9)). Increased age at diagnosis and male sex were associated with mortality in both subtypes. In UC but not Crohn's disease, a diagnosis after 1980 was associated with decreased mortality. CONCLUSIONS: In this population based study of IBD patients from North America, overall survival was similar to that expected in the US White population. Crohn's disease patients were at increased risk of dying from gastrointestinal disease and COPD whereas UC patients had a decreased risk of cardiovascular death.

Adult↗
PubMed2006

What's new: innovative concepts in inflammatory bowel disease.

Inflammatory bowel disease (IBD) has been the subject of recent intense research and development. A greater insight into the basic pathological mechanisms of ulcerative colitis (UC) and Crohn's disease (CD) has resulted in the emergence of more sophisticated and effective management options. Additionally, established therapies are attracting renewed interest with novel dosage regimens and new formulations offering improved efficacy whilst maintaining an excellent tolerance profile. High dose 5-aminosalicylic acid (5-ASA) has been a focus for investigation in recent clinical trials. The ASCEND study, which compared a 4.8 g/day dose with a 2.4 g/day dose, demonstrated that high dose mesalazine was significantly superior in achieving treatment success and symptom control, whilst maintaining a comparable tolerance and safety profile. The development of biotechnology agents targeted against tumour necrosis factor (TNF) provides promise of new treatment options in both CD and UC. The efficacy of CDP571, adalimumab and certolizumab have been investigated in CD, and infliximab, which is currently approved as an agent in inflammatory and fistulizing CD, has also been recently investigated in UC. Investigational pipeline molecules such as natalizumab, MLN-02, an anti-interleukin 12 antibody and sargramostim, have also shown encouraging results from early studies and are now undergoing evaluation in large clinical trials.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Total laparoscopic proctocolectomy with Brooke ileostomy: a novel incisionless surgical treatment for patients with ulcerative colitis.

BACKGROUND: This report describes the clinical benefits and safety of a novel (incisionless) laparoscopic operation for chronic ulcerative colitis. METHODS: The medical records for four patients with the diagnosis of chronic ulcerative colitis who underwent "incisionless" laparoscopic proctocolectomy with Brooke ileostomy were reviewed. A novel technique was used for successfully performance of four total proctocloectomies with end ileostomies that did not require abdominal incisions. The clinical outcomes measured included time to oral intake, time to ostomy output, operative time, postoperative and intraoperative complications, estimated blood loss, and length of stay. RESULTS: All the patients recovered without incident intraoperatively and postoperatively. The operative times ranged from 330 to 550 min. Postoperative findings included median time to oral intake (2 days), median time to ileostomy output (2 days), and median length of stay (4 days). CONCLUSION: This case series demonstrates that an incisionless approach to chronic ulocerative colitis for patients who desire an end ileostomy may be feasible and safe, offering patients short-term recovery and cosmetic benefits.

Aged↗
PubMed2005

Intentional infliximab use during pregnancy for induction or maintenance of remission in Crohn's disease.

AIM: To study the effects of infliximab on pregnancy and foetal outcome. METHODS: We conducted a retrospective chart review of women with Crohn's disease treated intentionally with infliximab during pregnancy. The primary outcome measure was the occurrence of congenital malformations. Secondary outcome measures were the rate of premature birth, low-birth weight, small for gestational age infants, intrauterine growth retardation and caesarean section. RESULTS: Ten women were identified. Eight women received maintenance infliximab infusions throughout their pregnancy and two women received their initial infliximab infusions during pregnancy. All 10 pregnancies ended in live births. No infants had congenital malformations, intrauterine growth retardation or small for gestational age parameters. Three infants were premature and one had low-birth weight. Eight women had a caesarean section. CONCLUSIONS: This is the first reported series of intentional infliximab use throughout pregnancy. These data, combined with other studies of inadvertent use of infliximab during pregnancy, suggest that the benefits of infliximab in achieving response and maintaining remission in mothers with Crohn's disease may outweigh the risk to the foetus of exposure to the drug. Further prospective data collection will be helpful to confirm these findings.

Abnormalities, Drug-Induced↗
PubMed2005

A randomized, double-blind, placebo-controlled trial of CDP571, a humanized monoclonal antibody to tumour necrosis factor-alpha, in patients with corticosteroid-dependent Crohn's disease.

AIM: To evaluate CDP571, a humanized monoclonal antibody to tumour necrosis factor-alpha, for the treatment of corticosteroid-dependent Crohn's disease. METHODS: Patients with corticosteroid-dependent Crohn's disease (use of prednisolone 15-40 mg/day or budesonide 9 mg/day for at least 8 weeks, a previous failed attempt to discontinue corticosteroids within 8 weeks, and Crohn's Disease Activity Index score 150 points or less) were enrolled in a 16-week, randomized, double-blind, placebo-controlled trial. The patients received intravenous CDP571 (20 mg/kg at week 0 and 10 mg/kg at week 8) or placebo. Corticosteroid therapy was decreased following a predefined schedule. The primary efficacy end-point was the percentage of patients with corticosteroid-sparing [i.e. no disease flare (Crohn's Disease Activity Index score > or =220 points) and no longer requiring corticosteroid therapy] at week 10. The major secondary efficacy end-point was corticosteroid-sparing at week 16. RESULTS: Seventy-one patients received treatment. Corticosteroid-sparing was achieved by 19 of 39 (48.7%) CDP571 patients and 13 of 42 (40.6%) placebo patients (P = 0.452) at week 10, and by 18 of 39 (46.2%) CDP571 patients and seven of 32 (21.9%) placebo patients (P = 0.032) at week 16. CDP571 therapy was well-tolerated and the incidence of serious adverse events was similar to placebo. CONCLUSIONS: The CDP571 was effective for corticosteroid-sparing at week 16 but not week 10, and was well-tolerated in patients with corticosteroid-dependent Crohn's disease.

Adult↗
PubMed2005

Budesonide as maintenance treatment in Crohn's disease: a placebo-controlled trial.

AIM: To assess the efficacy and safety of budesonide capsules 6 mg daily for prolongation of time to relapse and maintenance of remission in patients with Crohn's disease (CD) affecting the ileum and/or ascending colon. METHODS: In a double-blind, placebo-controlled, multicentre trial, 110 patients with CD, who had previously achieved remission in a placebo-controlled trial of budesonide 9 mg daily, were randomly assigned to receive budesonide 6 mg once daily or placebo for 52 weeks. Primary outcome measure was time to relapse [CD activity index (CDAI) of >150 plus an increase of at least 60 points from study entry or withdrawal due to clinical deterioration]. RESULTS: Median time to relapse was 360 days for budesonide patients; 169 days for placebo patients (P = 0.132). No significant differences were seen between groups in relapse rates at 1 year. Budesonide was safe and well tolerated, with a similar adverse events profile to placebo. CONCLUSION: Patients treated with budesonide 6 mg once daily had a trend towards a prolonged time to relapse and lower CDAI scores compared with patients treated with placebo, but relapse rates were not significantly different at the 1-year end point.

Adolescent↗
PubMed2005

PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis.

BACKGROUND: Inflammatory bowel disease associated with primary sclerosing cholangitis (PSC-IBD) may have a high prevalence of rectal sparing, backwash ileitis, and colorectal neoplasia. AIMS: To describe the clinical features and outcomes of PSC-IBD and compare these to a group of chronic ulcerative colitis (CUC) patients. METHODS: The medical records of all patients with PSC-IBD evaluated at the Mayo Clinic Rochester between 1987 and 1992 were abstracted for information on endoscopic and histological features, colorectal neoplasia, surgery, and other clinical outcomes. Patients referred for colorectal neoplasia and those who did not undergo colonoscopy with biopsies were excluded. A control group of CUC patients matched for sex, duration of IBD at first clinic visit, and calendar year of first clinic visit was identified, and similar information was abstracted. RESULTS: Seventy one PSC-IBD patients and 142 CUC patients without PSC were identified. Rectal sparing and backwash ileitis were more common in the PSC-IBD group (52% and 51%, respectively) than in controls (6% and 7%, respectively). Overall, colorectal neoplasia developed in 18 cases and 15 controls, including 11 cancers (seven cases and four controls). An increased risk of colorectal neoplasia or death was not detected in a matched analysis. Although the cumulative incidence of colorectal neoplasia was higher in cases (33%) than in controls (13%) at five years, this was of borderline statistical significance (p=0.054, unmatched log rank test). Overall survival from first clinic visit was significantly worse among cases (79% v 97%) at five years (p<0.001, unmatched log rank test). CONCLUSION: PSC-IBD is frequently characterised by rectal sparing and backwash ileitis. Colorectal neoplasia develops in a substantial fraction and overall survival is worse. PSC-IBD may represent a distinct IBD phenotype.

Adolescent↗
PubMed2004

Comparative pharmacokinetics of equimolar doses of 5-aminosalicylate administered as oral mesalamine (Asacol) and balsalazide: a randomized, single-dose, crossover study in healthy volunteers.

BACKGROUND: Existing pharmacokinetic data are insufficient to determine whether a delayed-release formulation of mesalamine (Asacol) results in greater systemic exposure to 5-aminosalicylic acid and its major metabolite N-acetyl-5-aminosalicylic acid than a prodrug (balsalazide). AIM: To determine the pharmacokinetic parameters of 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid from equimolar doses of 5-aminosalicylic acid administered as Asacol and balsalazide. METHODS: Nineteen healthy volunteers completed an open-label, single-dose, randomized, crossover study comparing the pharmacokinetics of 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid from equimolar doses of 5-aminosalicylic acid (800 mg) administered as Asacol (800 mg) and balsalazide (2250 mg). Plasma and urine samples were analysed for 5-aminosalicylic acid, N-acetyl-5-aminosalicylic acid, and balsalazide (urine only) using high-performance liquid chromatography methods with mass spectrometric detection. Pharmacokinetic parameters assessed for 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid included: percentage of dose excreted in urine (A(e)%), area under the plasma concentration-time curve (AUCt(last)); and maximum plasma concentration (C(max)). RESULTS: The geometric mean total (5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid) urinary excretion values (A(e)%) of Asacol and balsalazide were 19.26 and 19.31% (P = 0.98). The geometric mean A(e)% values of 5-aminosalicylic acid for Asacol and balsalazide were 0.39 and 0.37% (P = 0.78); the geometric mean A(e)% values of N-acetyl-5-aminosalicylic acid for Asacol and balsalazide were 18.78 and 18.83% (P = 0.98). The geometric mean 5-aminosalicylic acid AUC(t(last)) values for Asacol and balsalazide were 3295 and 3449 ng h/mL (P = 0.85); the geometric mean N-acetyl-5-aminosalicylic acid AUC(t(last)) values for Asacol and balsalazide were 15 364 and 16 050 ng h/mL (P = 0.69). The geometric mean 5-5-aminosalicylic acid C(max) values for Asacol and balsalazide were 319 and 348 ng/mL (P = 0.80); the geometric mean N-acetyl-5-aminosalicylic acid C(max) values for Asacol and balsalazide 927 and 1009 ng/mL (P = 0.67). CONCLUSIONS: The systemic absorption of 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid from Asacol and balsalazide are comparable based upon plasma pharmacokinetic parameters and urinary excretion values.

Administration, Oral↗
PubMed2004

CDP571, a humanised monoclonal antibody to tumour necrosis factor alpha, for moderate to severe Crohn's disease: a randomised, double blind, placebo controlled trial.

BACKGROUND: Targeting tumour necrosis factor alpha (TNF-alpha) has demonstrated efficacy in Crohn's disease. AIM: To evaluate CDP571, a humanised antibody to TNF-alpha, for treating active Crohn's disease. PATIENTS: A total of 396 patients with moderate to severe Crohn's disease. METHODS: In a 28 week, randomised, double blind, placebo controlled trial, patients received intravenous CDP571 (10 mg/kg) or placebo every eight weeks to week 24. The primary outcome measure was clinical response (a decrease in the Crohn's disease activity index (CDAI) to > or =100 points or remission (CDAI score < or =150 points)) at week 28. A secondary outcome measure was clinical response (using the same definition) at week 2. RESULTS: Clinical response occurred at week 28 in 80/263 (30.4%) CDP571 patients and 31/132 (23.5%) placebo patients (p = 0.102). Clinical response at week 2 occurred in 90/263 (34.2%) CDP571 patients and 28/132 (21.2%) placebo patients (p = 0.011). Post hoc exploratory subgroup analysis of 159 patients with baseline C reactive protein (CRP) > or =10 mg/l demonstrated significant differences between CDP571 and placebo in clinical response rates at weeks 2 (CDP571, 50/101 (49.5%); placebo, 9/58 (15.5%); p<0.001) and 28 (CDP571, 29/101 (28.7%); placebo, 7/58 (12.1%); p = 0.018). Adverse events occurred at similar frequencies in both treatment groups. CONCLUSIONS: CDP571 is modestly effective for short but not long term treatment of unselected patients with moderate to severe Crohn's disease. The clinical relevance of this short term effect is unclear. Post hoc analysis suggests both short and long term efficacy of CDP571 in patients with elevated baseline CRP (> or =10 mg/l). CDP571 is well tolerated.

Adult↗
PubMed2003

Review article: mild to moderate Crohn's disease--defining the basis for a new treatment algorithm.

Previously, clinicians have had few choices in treating mild to moderate Crohn's disease. They currently treat these Crohn's disease patients with oral mesalamine and antibiotics. This treatment approach is based on the safety of these agents, and the perception that they are effective. This perception regarding efficacy may be influenced by publication bias. This review examines the efficacy and safety data of the conventional corticosteroids, mesalamine, sulfasalazine, budesonide and antibiotics for inducing the remission of mild to moderate Crohn's disease from randomized controlled trials, and proposes an evidence-based treatment approach. Sulfasalazine has demonstrated modest efficacy when Crohn's disease is confined to the colon. Mesalamine has no clear benefit over placebo in treating active Crohn's disease. Conventional corticosteroids effectively induce remission but are associated with unwanted adverse effects. Budesonide has similar efficacy to conventional steroids with far fewer adverse effects. Antibiotics have not consistently demonstrated efficacy. We propose a new evidence-based approach which suggests inducing remission of mild to moderate Crohn's disease with budesonide 9 mg/day for patients with ileal and/or right colonic involvement; sulfasalazine for those with disease limited to the colon; and conventional steroids for high disease activity, those who failed budesonide and those with left-sided disease who are allergic or intolerant to sulfasalazine.

Administration, Topical↗