Patient adherence and efficacy of certolizumab pegol in the management of Crohn's disease.

Treatment with Anti-Tumor Necrosis Factor (anti-TNF) therapy has become a mainstay of therapy for patients with CD who are unresponsive to conventional medical management. Currently there are three anti-TNFα antibodies that have been approved by the US Food and Drug Administration for the treatment of CD, namely infliximab, adalimumab and certolizumab pegol (CZP). Several double blind placebo controlled trials determined that CZP is effective as induction and maintenance treatment in adult patients with CD regardless of their prior exposure to other anti-TNFα antibodies.

Developing an instrument to assess the endoscopic severity of ulcerative colitis: the Ulcerative Colitis Endoscopic Index of Severity (UCEIS).

Background: Variability in endoscopic assessment necessitates rigorous investigation of descriptors for scoring severity of ulcerative colitis (UC).

Objective: To evaluate variation in the overall endoscopic assessment of severity, the intra- and interindividual variation of descriptive terms and to create an Ulcerative Colitis Endoscopic Index of Severity which could be validated.

Design: A two-phase study used a library of 670 video sigmoidoscopies from patients with Mayo Clinic scores 0-11, supplemented by 10 videos from five people without UC and five hospitalised patients with acute severe UC.

Early symptomatic response and mucosal healing with mesalazine rectal suspension therapy in active distal ulcerative colitis--additional results from two controlled studies.

Background: Rapid resolution of symptoms and endoscopic inflammation in ulcerative colitis (UC) represent important treatment goals.

Aims: To establish times to bleeding cessation and endoscopic healing for topical and oral mesalazine in active distal UC, a post hoc analysis of two published studies was performed.

Methods: Study I (Sutherland 1987) compared mesalazine rectal suspension to placebo, while Study II (Safdi 1997) compared topical suspensions, either alone or in combination with oral mesalazine, and oral alone.

The London position statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organisation: safety.

This paper in the series from the World Congress of Gastroenterology addresses the safety and immunogenicity of biological therapy. The safety profile in randomized controlled studies of all biological agents in Crohn's disease (CD) and ulcerative colitis has been generally favorable, but a small percentage of patients experience severe side effects on biological therapy, including pneumonia, tuberculosis, lymphoma, demyelination, drug-induced lupus, or hepatotoxicity. Although there is unequivocal evidence of an increased risk of serious infection among patients with rheumatoid arthritis treated with anti-tumor necrosis factor therapy, the evidence is less clear in CD.

Update on the management of Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory disorder characterized by focal, asymmetric, transmural inflammation of any part of the luminal gastrointestinal tract of uncertain etiology and an unpredictable course. The available treatment options include aminosalicylates, budesonide and systemic corticosteroids, antibiotics, immunomodulators,methotrexate and anti-TNF agents. This review discusses recent developments in the treatment of CD and provides a comprehensive update on management of patients with CD based on the data from randomized controlled trials.

No increased risk of myocardial infarction among patients with ulcerative colitis or Crohn's disease.

Background & Aims: Patients with chronic inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, and psoriasis have an increased risk of myocardial infarction (MI). Studies of the risk of MI among patients with inflammatory bowel disease have provided inconsistent results. We aimed to determine the risk of first-time acute MI in patients with ulcerative colitis (UC) or Crohn's disease (CD) compared with patients from general practice.

Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis.

Background & Aims: In the Active Ulcerative Colitis Trial (ACT)-1 and ACT-2, patients with ulcerative colitis treated with infliximab were more likely than those given placebo to have a clinical response, undergo remission, and have mucosal healing. We investigated the association between early improvement (based on endoscopy) and subsequent clinical outcome.

Methods: Patients underwent endoscopic evaluations at weeks 0, 8, 30, and 54 (ACT-1 only), and were categorized into 4 subgroups by week 8 (Mayo endoscopy subscore, 0-3).

Inflammatory bowel disease therapy: current state-of-the-art.

Purpose Of Review: The aim of this article is to review current evidence-based approaches to treatment of ulcerative colitis and Crohn's disease.

Recent Findings: The primary goal of treatment is to induce and to maintain remission in a safe and efficacious fashion. The 5-aminosalicylic acid (5-ASA) agents and oral steroids remain the first-line approach for the treatment of ulcerative colitis and Crohn's disease.

Long-term infliximab maintenance therapy for ulcerative colitis: the ACT-1 and -2 extension studies.

Background: The aim was to evaluate long-term efficacy, quality of life, and safety in ulcerative colitis patients who received infliximab during the ACT-1 and -2 extension studies.

Methods: Adults with moderate-to-severely active ulcerative colitis in the 54-week ACT-1 and 30-week ACT-2 studies who achieved benefit from infliximab were eligible to participate in extension studies and receive up to 3 additional years of therapy. Patients received randomized study medication until all sites were unblinded; placebo-treated patients were discontinued.

Combination of genetic and quantitative serological immune markers are associated with complicated Crohn's disease behavior.

Background: Treatment of Crohn's disease (CD) with biologics may alter disease progression, leading to fewer disease-related complications, but cost and adverse event profiles often limit their effective use. Tools identifying patients at high risk of complications, who would benefit the most from biologics, would be valuable. Previous studies suggest that biomarkers may aid in determining the course of CD.

Review article: delivery and efficacy of topical 5-aminosalicylic acid (mesalazine) therapy in the treatment of ulcerative colitis.

Background: The use of topical therapy in the treatment of ulcerative colitis has declined in recent years despite evidence of good efficacy.

Aims: To review US prescription trends for 5-aminosalicylic acid (5-ASA) since the US approval of Asacol extended-release oral mesalazine (mesalamine) in 1992; to estimate the optimal level of 5-ASA exposure in the distal colon; to determine factors influencing distal colonic exposures; and to compare the effectiveness of different 5-ASA formulations (oral, topical suspension, foam, suppositories) in clinical trials.

Methods: Review of clinical trials, physiologic studies and prescription trends of various mesalazine formulations for treatment of distal ulcerative colitis.

Randomised clinical trial: delayed-release oral mesalazine 4.8 g/day vs. 2.4 g/day in endoscopic mucosal healing--ASCEND I and II combined analysis.

Background: Recent studies have focused on the importance of mucosal healing in ulcerative colitis (UC). However, it was still unclear whether higher doses of delayed-release mesalazine (mesalamine) could provide additional benefit.

Aim: To examine how two doses of delayed-release mesalazine (4.

Clinical pharmacology of 5-ASA compounds in inflammatory bowel disease.

Mesalamine has been the first-line of therapy in patients with inflammatory bowel disease (IBD) since the 1960s. This article serves as a review of the different 5-aminosalicylic acid compounds, release formulations, use and dosing in the treatment of IBD, in particular ulcerative colitis.

Clinical trial: once-daily mesalamine granules for maintenance of remission of ulcerative colitis - a 6-month placebo-controlled trial.

Background: Ulcerative colitis (UC) is a chronic relapsing and remitting idiopathic inflammatory bowel disorder.

Aim: To evaluate once-daily mesalamine (mesalazine) granules (MG) for maintenance of remission of UC.

Methods: Randomized, double-blind, placebo-controlled trial of patients (n=209 MG, n=96 placebo) with UC in remission [revised Sutherland Disease Activity Index (SDAI) rectal bleeding=0, mucosal appearance <2] who took MG 1.

A systematic review of factors that contribute to hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease.

Background & Aims: Hepatosplenic T-cell lymphoma (HSTCL) is a rare and usually fatal lymphoma that primarily affects men younger than 35 years old. Treatment of patients with inflammatory bowel disease (IBD) using antibodies to tumor necrosis factor (anti-TNFs) and thiopurines has been associated with HSTCL. We investigated the medications, duration of therapy, and ages of patients associated with HSTCL.

5-ASA Dose-Response: Maximizing Efficacy and Adherence.

Mesalamine (5-aminosalicylic acid; 5-ASA) represents the cornerstone of first-line therapy for mild-to-moderate ulcerative colitis (UC). Current guidelines suggest that the combination of oral and rectal therapies provide optimal symptom resolution and effectively maintain remission in the majority of these patients. Although effective, most oral 5-ASA formulations have a high pill burden and rectal therapies are associated with low adherence.

Emerging prognostic markers to determine Crohn's disease natural history and improve management strategies: a review of recent literature.

Because Crohn's disease (CD) is a chronic, incurable condition, patients require life-long therapeutic approaches to initiate and maintain symptom control, improve quality of life, avoid hospitalizations and surgery, and minimize short- and long-term toxicity and complications such as stricturing, fistulae, osteoporosis and associated bony fractures, and linear growth failure in pediatric patients. Many physicians use symptom-based classifications, such as those published in the American College of Gastroenterology Practice Guidelines, to classify disease severity. However, all current classifications for CD focus predominantly on treating the present symptoms and not on the long-term treatment goal of altering the natural history of the disease.

A prospective, randomized, comparative trial evaluating respiratory depression during patient-controlled versus anesthesiologist-administered propofol-remifentanil sedation for elective colonoscopy.

Background: Patient-controlled sedation (PCS) with propofol-remifentanil (PR) is associated with rapid sedation and recovery, but it is associated with a greater requirement for airway rescue than PCS with midazolam-fentanyl.

Objective: To demonstrate that respiratory depression associated with PR is more frequent during anesthesiologist-administered sedation (AAS) than during PCS.

Design: Prospective, randomized, open-label study.

An approach to the management of refractory ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology associated with dysregulation of the gastrointestinal mucosal immune system. It is characterized by a waxing and waning course and approximately 15% of UC patients will experience a severe episode. The first line treatment for severe colitis includes IV corticosteroids, however, 40% of patients are non-responsive to corticosteroid therapy and may require either colectomy, intravenous infliximab or intravenous cyclosporine within 3-5 days of presentation.

Reinduction with certolizumab pegol in patients with relapsed Crohn's disease: results from the PRECiSE 4 Study.

Background & Aims: We sought to determine the efficacy of certolizumab pegol reinduction in patients with active Crohn's disease who respond to induction therapy with certolizumab pegol and then relapse during continuous or interrupted maintenance therapy.

Methods: In the Pegylated Antibody Fragment Evaluation in Crohn's Disease: Safety and Efficacy (PRECiSE) 2 trial, 428 patients who responded to induction therapy with certolizumab pegol at week 6 were randomized to continuous therapy with certolizumab pegol or placebo (drug interruption) during weeks 6 to 26. Patients who relapsed before week 26 could enter PRECiSE 4, an ongoing open-label extension trial in which patients on continuous therapy underwent recapture with a single extra 400-mg dose of certolizumab pegol, and patients who relapsed after drug interruption underwent reinduction with certolizumab pegol 400 mg at weeks 0, 2, and 4 followed by maintenance with certolizumab pegol 400 mg every 4 weeks.

What is the optimal therapy for Crohn's disease: step-up or top-down?

Crohn's disease (CD) is an idiopathic chronic inflammatory disorder of the digestive tract, which is incurable. Present therapeutic guidelines follow a sequential step-up approach that focuses on treating acute disease or 'inducing clinical remission' and subsequently aims to 'maintain clinical response'. In view of the chronic relapsing-remitting disabling disease course, new treatment approaches have been sought with the ultimate end point of disease course modification and mucosal healing.

Continuous therapy with certolizumab pegol maintains remission of patients with Crohn's disease for up to 18 months.

Background & Aims: The safety and efficacy of maintenance therapy with the anti-tumor necrosis factor certolizumab pegol has not been reported beyond 6 months. We assessed the long-term efficacy, safety, and immunogenicity of continuous versus interrupted maintenance therapy with subcutaneous certolizumab pegol in patients with Crohn's disease.

Methods: Patients who responded to induction therapy at week 6 of the PEGylated Antibody Fragment Evaluation in Crohn's Disease: Safety and Efficacy (PRECiSE) 2 trial were assigned randomly to groups given certolizumab pegol (continuous) or placebo (drug-interruption) during weeks 6 to 26.