The incidence of ulcerative colitis (UC) is high. Despite the availability of various therapeutic agents for the treatment of UC, the routine treatment has limitations and serious side effects. Therefore, a new drug that safely and effectively treats UC is urgently needed. Polysaccharides from natural resources have recently become a hot topic of study for their therapeutic effects on UC. These effects are associated with the regulation of inflammatory cytokines, intestinal flora, and immune system and protection of the intestinal mucosa. This review focuses on the recent advances of polysaccharides from natural resources in the treatment of UC. The mechanisms and practicability of polysaccharides, including pectin, guar gum, rhamnogalacturonan, chitosan, fructan, psyllium, glycosaminoglycan, algal polysaccharides, polysaccharides from fungi and traditional Chinese medicine, and polysaccharide derivatives, are discussed in detail. The good efficacy and safety of polysaccharides make them promising drugs for treating UC.

There is no cure for Crohn disease. Newer treatments, such as biological therapy, have led to an improved quality of life. This article focuses on the surgical management of Crohn disease of the colon, rectum, and anus. Restorative and nonrestorative surgical options for colonic Crohn disease are discussed. Treatment options for perianal Crohn disease are also reviewed.

Crohn's disease (CD) impairs patients' health-related quality of life (HRQoL), therefore a goal of treatment is to improve their health. Recently, a more ambitious therapeutic target has been proposed, to reestablish patients' HRQoL to normal standards. There is no information on long-term prognostic value of restoring the health of patients with CD. Our aim was to determine if early restoration of HRQoL with antitumor necrosis factor (anti-TNF) agents is associated with long-term clinical remission.

Retrospective longitudinal study in patients with active CD treated with anti-TNF agents. Patients completed the Inflammatory Bowel Disease Questionnaire (IBDQ)-36 at baseline and weeks 2, 6, 14, 28, and 52. Early restoration of health was defined as an IBDQ-36 score > 209 at week 14, and long-term clinical remission as a Cohn's disease activity index (CDAI) score < 150 maintained through week 52.

Ninety-four patients were included. Sixty-three patients maintained long-term remission, with 47 (75%) of them achieving early restoration of HRQoL. Of the 31 patients who did not maintain long-term remission, only 4 (13%) restored their HRQoL early (P < 0.01). There was a strong negative correlation between the IBDQ-36 at week 14 and CDAI values at week 52 (rs = - 0.64, P < 0.01). Ninety-two percent of patients with early restoration of HRQoL maintained long-term remission versus 37% who did not restore their HRQoL (P < 0.01). To predict long-term remission, the cutoff point of 209 of the early IBDQ-36 had an area under the receiver operating characteristic (AUROC) curve of 0.87.

Achieving early restoration of HRQoL with anti-TNF agents is associated with sustained long-term remission. This could be a therapeutic goal of treatment in clinical trials and daily practice.

Utilization trends and health effects of infliximab and adalimumab in inflammatory bowel disease (IBD) are incompletely understood. We aimed to describe utilization trends of these 2 anti-tumor necrosis factor (TNF) agents, determine the correlation between utilization with rates of hospitalization and surgery and describe differences in use between adults and children.

Longitudinal data were analyzed for drug utilization, hospitalization, and abdominal surgery. Descriptive statistics were used to show trends, and utilization quotients were compared for standardization. Multivariate logistic regression analysis assessed the association between drug use and rates of hospitalization and surgery.

Four hundred thirty-eight pediatric and 2514 adult patients with IBD generated a total of 51,882 inpatient and outpatient encounters, representing 1185 Crohn's disease, 1531 ulcerative colitis, and 236 indeterminate colitis patients. From 2007 through 2012, utilization quotients declined for hospitalization but remained unchanged for surgery; adalimumab saw a 3-fold increase, despite continued dominance of infliximab. Median band and mean fitted plots showed downward hospitalization trends from 2006 to 2012. Utilization of infliximab peaked in 2008, Q4 with gradual decline to 2012, Q2; and adalimumab showed moderate increased utilization since 2007, Q1. Use of infliximab (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.70-0.83) and adalimumab (OR, 0.79; 95% CI, 0.72-0.87) was associated with decreased hospitalization risk but not associated with reduced abdominal surgery risk. Children had increased hospitalization (OR, 2.68; 95% CI, 2.49-2.88) but decreased risk for abdominal surgery (OR, 0.57; 95% CI, 0.46-0.70).

Current infliximab use remains substantially greater than adalimumab use, despite recent increased use of adalimumab. Although trends for hospitalization for IBD are decreasing, it is not reflected in abdominal surgery rates in a tertiary IBD referral center.

Crohn's disease negatively affects patients' quality of life and ability to work. We investigated the impact of adalimumab on work productivity, daily activities, and quality of life in an open-label trial (N=945). The population comprised both infliximab-naïve and -exposed patients, including infliximab primary non-responders.

Patients received adalimumab induction therapy (160 mg/80 mg at Weeks 0/2), followed by adalimumab 40 mg every other week for up to 20 weeks (patients with flares/non-response could receive 40 mg weekly at/after Week 12). The Work Productivity and Activity Impairment Questionnaire and Short Inflammatory Bowel Disease Questionnaire were assessed. Indirect cost savings were estimated based on the average work productivity improvements at Week 20.

Mean baseline scores indicated severe productivity impairment and poor quality of life. At Week 20, 60% of infliximab-naïve and 47% of infliximab primary non-responders achieved clinically important improvements (≥9 points) on the Short Inflammatory Bowel Disease Questionnaire, and 51% and 43%, respectively, achieved the minimum clinically important difference (improvement ≥7 percentage points) for total work productivity impairment (non-responder imputation). At Week 20, 64% of infliximab-naïve and 55% of infliximab primary non-responders achieved clinically important improvements in total activity impairment. Estimated 20-week total indirect productivity-related cost savings were €3070 per infliximab-naïve patient and €2059 per infliximab-exposed patient.

Adalimumab therapy significantly improved work productivity and disease-specific quality of life for patients with moderate to severe Crohn's disease. Patients who failed prior infliximab therapy and patients naïve to infliximab benefited from adalimumab, with potentially greater benefits for infliximab-naïve patients (NCT00409617).

To assess the effect of adalimumab on work productivity and indirect costs in patients with Crohn's disease (CD) using a meta-analysis of clinical trials.

Study-level results were pooled from all clinical trials of adalimumab for moderate to severe CD in which work productivity outcomes were evaluated. Work Productivity and Activity Impairment Questionnaire outcomes (absenteeism, presenteeism and total work productivity impairment [TWPI]) were extracted from adalimumab trials. Meta-analyses were used to estimate pooled averages and 95% CIs of one-year accumulated reductions in work productivity impairment with adalimumab. Pooled averages were multiplied by the 2008 United States national average annual salary ($44,101) to estimate per-patient indirect cost savings during the year following adalimumab initiation.

The four included trials (ACCESS, CARE, CHOICE and EXTEND) represented a total of 1202 employed adalimumab-treated patients at baseline. Each study followed patients for a minimum of 20 weeks. Pooled estimates (95% CIs) of one-year accumulated work productivity improvements were as follows: -9% (-10% to -7%) for absenteeism; -22% (-26% to -18%) for presenteeism; and -25% (-30% to -20%) for TWPI. Reductions in absenteeism and TWPI translated into per-patient indirect cost savings (95% CI) of $3,856 ($3,183 to $4,529) and $10,964 ($8,833 to $13,096), respectively.

Adalimumab provided clinically meaningful improvements in work productivity among patients with moderate to severe CD, which may translate into substantial indirect cost savings from an employer's perspective.

Crohn's disease patients have a decreased Quality of Life (QoL) which is in part due to extreme fatigue. In a pilot study we prospectively assessed the feasibility and effect of psychological interventions in the management of fatigue.

Patients with quiescent Crohn's disease and a high fatigue score according to the Checklist Individual Strength were randomized to Problem Solving Therapy (PST), Solution Focused Therapy (SFT) or to a control group (treatment as usual, TAU). Patients completed the Inflammatory Bowel Disease Questionnaire, the EuroQol-5D, and the Trimbos questionnaire for Costs.

Twenty-nine patients were included (12 TAU, 9 PST, 8 SFT), of these 72% were female, mean age was 31 years (range 20-50). The SFT group improved on the fatigue scale in 85.7% of the patients, in the PST group 60% showed improved fatigue scores and in the TAU group 45.5%. Although not significant, in both intervention groups the QoL increased. Medical costs lowered in 57.1% of the patients in the SFT group, in the TAU 45.5% and the in PST group 20%. The drop out rate was highest in the PST group (44%; SFT 12.5%; TAU 8.3%).

PST and SFT both positively affect the fatigue and QoL scores in patients with Crohn's disease. SFT seems most feasible with fewer dropouts and is therefore a promising new tool in the management of fatigue in Crohn's disease patients.

No validated instruments have been developed to measure work disability in Crohn's disease (CD). The aim of our study was to develop and validate a CD perceived work disability questionnaire (CPWDQ).

Development phase: an initial questionnaire containing 52 items was obtained from patients' interviews plus additional sources; it was completed by 106 patients and the 16 most significant items were selected using a psychometric method in order to create the CPWDQ. Validation phase: The validation assessed the questionnaire's convergent validity, discriminant validity, test-retest reproducibility, and internal consistency in 108 patients. Spearman rank correlation, t-test, intraclass correlation, and Cronbach's alpha were used for the analysis.

Convergent validity was confirmed by good correlations between the CPWDQ and: clinical activity (r = 0.59, P < 0.01), the Short Inflammatory Bowel Disease Questionnaire, IBDQ-9, (r = 0.76, P < 0.001), Euroqol-5D (r = 0.53, P < 0.01), and overall work impairment (WPAI_CD) r = 0.66 (P < 0.01). Discriminant validity: CPWQ scores were higher in patients expected to have more severe disability, that is, in patients with active disease (n = 38) 32.3 ± 7.3 versus inactive (n = 70) 22.6 ± 5.9 (P < 0.001), in those requiring previous sick leave 30.7 ± 7.5 (n = 45) versus no sick leave 22.6 ± 6.6 (n = 63) (P < 0.01), and in those requiring hospitalization 32.2 ± 8.6 (n = 18) versus no hospitalization 24.7 ± 7.1 (n = 90) (P < 0.01). Internal consistency was also good (Cronbach's alpha = 0.89). Reproducibility: CPWDQ measures obtained 2 weeks apart showed an excellent intraclass correlation coefficient: 0.89 (95% CI: 0.83-0.93).

The CPWDQ seems to be a valid, reliable tool for measuring subjective work disability in CD.

To review certolizumab pegol for the treatment of moderate-to-severe Crohn's disease (CD).

Clinical studies were identified through MEDLINE (1966-October 1, 2009), bibliographies of articles, International Pharmaceutical Abstracts, clinicaltrials.gov, fda.gov, and New Drug Approval documents (www.accessdata.fda.gov). Search terms were CDP 870, certolizumab pegol, Cimzia, Crohn's disease, and inflammatory bowel disease.

Human studies describing pharmacology, pharmacokinetics, efficacy, and safety of certolizumab pegol were identified. Phase 2 and Phase 3 randomized controlled trials and observational studies were reviewed, with emphasis given to Phase 2 and Phase 3 trials.

Certolizumab pegol is a tumor necrosis factor-alfa (TNF-alpha) antagonist, approved for the treatment of moderate-to-severe CD that is failing conventional therapy. It is an antigen-binding fragment (Fab') portion of an immunoglobulin G antibody attached to a polyethylene glycol moiety. In 2 Phase 3 randomized, placebo-controlled trials, certolizumab pegol was effective in inducing clinical response compared with placebo. Common adverse effects during clinical trials were upper respiratory tract infection, urinary tract infection, and arthralgia. Serious infection occurred in 3% of patients. The 4 published controlled trials for the use of certolizumab pegol in the treatment of CD share similar limitations with other studies of TNF-alpha antagonists including high placebo response, natural course of disease fluctuation, and the use of Crohn's Disease Activity Index to assess outcomes. However, certolizumab pegol is an effective agent for adults with moderate-to-severe CD with less than optimal response to conventional therapy. Long-term efficacy and safety data are unavailable. Certolizumab pegol and adalimumab, unlike infliximab, can be self-administered.

With similarity in cost and the lack of head-to-head comparisons, patient and physician preference may determine choice of TNF-alpha antagonist.

Infliximab is a chimeric immunoglobulin G1kappa monoclonal antibody that binds with high affinity and specificity to the soluble form of tumor necrosis factor (TNF)-alpha, preventing it from binding to cellular receptors. Infliximab also binds to membranebound TNF-alpha found on inflammatory cell surfaces, inducing apoptosis. Currently, infliximab is used for the induction and maintenance of remission in Crohn's disease (CD), with documented success. Infliximab's efficacy in the treatment of ulcerative colitis (UC) is now being investigated due to the similarities in the pathophysiology of CD and UC.

The aim of this study was to review and evaluate the current literature of infliximab use in steroid-refractory UC to assess its role in treatment.

A search of MEDLINE was conducted (1950-November 2007). Key terms included, but were not limited to, infliximab, inflammatory bowel disease, ulcerative colitis, cost, and quality of life. Studies included for review were limited to English-language, full-text, randomized, double-blind, placebo-controlled trials. Clinical trials were reviewed and summarized.

Four controlled clinical trials of infliximab in the treatment of steroid-refractory UC were found and assessed. In a double-blind, randomized, controlled trial in 43 patients with moderately severe, glucocorticoid-resistant UC, infliximab and placebo were not significantly different with respect to clinical and sigmoidoscopic remission or quality of life 2 and 6 weeks after infliximab treatment. In a multicenter, randomized, double-blind, placebo-controlled study in 45 patients with moderately severe to severe glucocorticoid-resistant UC, infliximab was associated with a significantly reduced need for colectomy compared with placebo (29% vs 67%; P=0.017). The Active Ulcerative Colitis Trials (ACT) 1 and 2 together included 728 patients with moderate to severe glucocorticoid-resistant UC. The primary outcome, the rate of clinical response at 8 weeks, was significantly higher with infliximab compared with placebo (5 mg/kg: ACT 1, 69.4%, ACT 2, 64.5%; 10 mg/kg: ACT 1, 61.5%, ACT 2, 69.2%; placebo: ACT 1, 37.2%;, ACT 2, 29.3%; all, P < 0.001 vs placebo). Based on the data from ACT 1 and 2, infliximab was associated with improved health-related quality-of-life (HRQOL) scores based on the Inflammatory Bowel Disease Questionnaire and the 36-item Short Form Health Survey.

Current data suggest that infliximab is an effective alternative treatment option for patients with moderate to severe UC with an inadequate response to conventional glucocorticoid treatment. Further trials are needed to assess infliximab's impact on the treatment and progression of UC, the HRQL of patients with UC, and the economic impact on the health care system.

The most important factors that determine treatment strategy in ulcerative colitis (UC) are disease extent and severity. Orally-topically administered 5-aminosalicylates (5-ASA) remain the treatment of choice in mild-to-moderate UC. In contrast, the treatment of refractory (to steroids, azathioprine or 5-ASA) and fulminant cases is still demanding. New evidence supports a role for infliximab induction and/or maintenance therapy in these subgroup of patients leading to increased remission and decreased colectomy rates. The aim of this paper is to review the rationale for the use of TNF-alpha inhibitors in the treatment of UC.