Discontinuation of Infliximab Therapy in Patients with Crohn's Disease.

BACKGROUND: Whether infliximab therapy can be successfully discontinued after patients with Crohn’s disease have attained sustained, clinical, biochemical, and endoscopic remission is unknown. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled withdrawal study of infliximab in patients with Crohn’s disease who were in clinical, biochemical, and endoscopic remission after standard infliximab maintenance therapy for at least 1 year. Patients were randomly assigned 1:1 to continue infliximab therapy or to receive matching placebo for 48 weeks.

Outcomes After Primary Infliximab Treatment Failure in Inflammatory Bowel Disease.

Background: Primary infliximab treatment failure is common in patients with inflammatory bowel disease and represents a challenge to clinicians. Treatment options are limited. This study assessed the prognosis, defined as surgery-free survival, in patients with primary infliximab treatment failure as compared to patients without primary failure (initial responders).

Magnitude of Increased Infliximab Clearance Imposed by Anti-infliximab Antibodies in Crohn's Disease Is Determined by Their Concentration.

Antibodies (Abs) against infliximab (IFX) increase IFX clearance and can result in treatment failure and acute hypersensitivity reactions. However, interpretation of their clinical value is complicated by individual differences in Ab responses and methods used for quantification. The increase in IFX clearance imposed by anti-IFX Abs has generally been evaluated using a binary classification, i.

Immunosuppressive drugs impairs antibody response of the polysaccharide and conjugated pneumococcal vaccines in patients with Crohn's disease.

Background: Patients with Crohn's disease (CD) have a higher risk of infectious diseases including pneumococcal infections, and the risk increases with immunotherapy. The primary endpoint of this study was to investigate the specific antibody response to two pneumococcal vaccines in CD patients with and without immunosuppressive treatment four weeks post vaccination.

Methods: In a randomized trial of the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent pneumococcal conjugated vaccine (PCV13), a group of CD patients treated with immunosuppressive drugs (IS) alone or in combination with TNF-α antagonists were compared to a group of CD patients not treated with any of these drugs (untreated).

Implications of Infliximab Treatment Failure and Influence of Personalized Treatment on Patient-reported Health-related Quality of Life and Productivity Outcomes in Crohn's Disease.

Background: This study assessed the effects of infliximab (IFX) treatment failure on patient-reported outcomes and explored the influence of using personalized treatment in this situation.

Methods: Sixty-nine Crohn's disease patients with IFX treatment failure were randomized to an intensified IFX regimen (n = 36) or personalized treatment defined by IFX and anti-IFX antibodies (n = 33). Health-related quality of life evaluated with the Short Inflammatory Bowel Disease Questionnaire (IBDQ) and productivity evaluated with the Work Productivity and Activity Impairment Questionnaire (WPAI:CD) were assessed at treatment failure and after 4, 8, 12 and 20 weeks.

Time Course and Clinical Implications of Development of Antibodies Against Adalimumab in Patients With Inflammatory Bowel Disease.

Background: Antibodies (Abs) against adalimumab (ADL) have been associated with low ADL levels and treatment failure.

Aim: To characterize the temporal characteristics of anti-ADL Ab appearance and possible disappearance, and determine the clinical significance on drug efficacy and disease course.

Methods: Cohort study including inflammatory bowel disease patients in whom anti-ADL Abs had been assessed by radioimmunoassay (RIA) and, in case of disappearance, by enzyme immunoassay, and functional reporter gene assay.

Systematic Information to Health-Care Professionals about Vaccination Guidelines Improves Adherence in Patients With Inflammatory Bowel Disease in Anti-TNFα Therapy.

Objectives: Implementation of guidelines for prevention of infectious diseases during anti-TNFα therapy in patients with inflammatory bowel disease (IBD) is important but difficult. We investigated whether systematic information to health-care professionals about these guidelines improves patients' adherence.

Methods: The study comprised three parts: (1) cross-sectional evaluation of baseline vaccination status in all IBD patients in anti-TNFα therapy (reference group; n=130); (2) prospective interventional study, where health-care professionals received systematic oral and written information about vaccination guidelines at baseline and at 2-month intervals for 6 months, followed by reassessment of vaccination status (intervention group; n=99); (3) cross-sectional evaluation of representative gastroenterologists' knowledge of guidelines (n=53).

Individualized Therapy Is a Long-Term Cost-Effective Method Compared to Dose Intensification in Crohn's Disease Patients Failing Infliximab.

Background: In Crohn's disease patients failing infliximab therapy, interventions defined by an algorithm based on infliximab and anti-infliximab antibody measurements have proven more cost-effective than intensifying the infliximab regimen.

Aim: This study investigated long-term economic outcomes at the week 20 follow-up study visit and after 1 year. Clinical outcomes were assessed at week 20.

Changes in serum trough levels of infliximab during treatment intensification but not in anti-infliximab antibody detection are associated with clinical outcomes after therapeutic failure in Crohn's disease.

Background And Aims: Intensification of the infliximab (IFX) regimen is recommended if the treatment effect is inadequate. However, the rationale for this is not well defined as the underlying mechanisms vary. The aim of this study was to explore the association between changes in serum IFX and anti-IFX antibodies (Abs) after IFX intensification and clinical outcomes.

Colonoscopy surveillance for dysplasia and colorectal cancer in patients with inflammatory bowel disease.

The risk of colorectal cancer (CRC) and dysplasia in patients with inflammatory bowel disease (IBD) has been highly debated as risk estimates from different studies vary greatly. The present national Danish guideline on colonoscopy surveillance for dysplasia and colorectal cancer in patients with IBD is based on a thorough review of existing literature with particular focus on recent studies from Denmark revealing a lower risk of CRC than previously assumed. The overall risk of CRC in the Danish IBD population does not appear to be different from that of the background population; however, in some subgroups of patients the risk is increased.

Discontinuation of infliximab therapy in patients with Crohn's disease in sustained complete remission (the STOP IT study): protocol for a double-blind, randomised, placebo-controlled, multicentre trial.

Introduction: Infliximab (IFX), a monoclonal chimeric antibody against tumour necrosis factor (TNF) α, is effective for induction and maintenance of remission in moderate to severe Crohn's disease. Discontinuation of IFX maintenance therapy in patients in remission should be considered in order to reduce the potential long-term side effects and lower costs.

Methods And Analysis: This is a prospective, double-blind, randomised, placebo-controlled, multicentre study of patients with luminal Crohn's disease who have been treated with IFX for at least 1 year and are in sustained complete clinical, biochemical and endoscopic remission (ie, Crohn's Disease Activity Index (CDAI) score <150, complete mucosal healing and biochemical markers of inflammation within the normal range).

Antibodies against infliximab are associated with de novo development of antibodies to adalimumab and therapeutic failure in infliximab-to-adalimumab switchers with IBD.

Background: A notable proportion of patients with inflammatory bowel disease (IBD) are switched from infliximab (IFX) to adalimumab (ADL). We investigated if immunogenicity of IFX influenced immunogenicity and clinical outcomes of later ADL therapy.

Methods: Single-center cohort study including all patients with IBD assessed for antibodies (Abs) against IFX or ADL.

Clinical implications of measuring drug and anti-drug antibodies by different assays when optimizing infliximab treatment failure in Crohn's disease: post hoc analysis of a randomized controlled trial.

Objectives: Cost-effective guidance of therapeutic strategy in Crohn's disease patients with secondary infliximab (IFX) treatment failure may be achieved by serum IFX and anti-IFX antibody (Ab) measurements by radioimmunoassay (RIA). This study investigated implications of using other techniques for this purpose.

Methods: This is a post hoc analysis of randomized clinical trial including 66 Crohn's disease patients with IFX failure in whom IFX and anti-IFX Ab measurements by RIA had been used for therapeutic guidance.

Individualised therapy is more cost-effective than dose intensification in patients with Crohn's disease who lose response to anti-TNF treatment: a randomised, controlled trial.

Objective: Although the reasons for secondary loss of response to infliximab (IFX) maintenance therapy in Crohn's disease vary, dose intensification is usually recommended. This study investigated the cost-effectiveness of interventions defined by an algorithm designed to identify specific reasons for therapeutic failure.

Design: Randomised, controlled, single-blind, multicentre study.

Comparison of techniques for monitoring infliximab and antibodies against infliximab in Crohn's disease.

Background: Several techniques are used to measure infliximab (IFX) and anti-IFX antibodies (Abs) in Crohn's disease. The aim of this study was to compare different assays for this purpose.

Methods: Fluid-phase radioimmunoassay (RIA), solid-phase enzyme-linked immunosorbent assay (ELISA), reporter gene assay (RGA), and enzyme immunoassay (EIA; anti-IFX Ab only) were assessed.

Clinical implications of variations in anti-infliximab antibody levels in patients with inflammatory bowel disease.

Background: The aim of the study was to investigate variations in anti-infliximab (IFX) antibody (Ab) levels and clinical implications thereof in patients with inflammatory bowel disease (IBD).

Methods: A retrospective, explorative, single-center study of patients with IBD who developed anti-IFX Ab and in whom anti-IFX Ab were reassessed.

Results: IFX was administered to 316 patients; anti-IFX Ab was determined in 180 patients and detected in 83 (46%).

Acute and delayed hypersensitivity reactions to infliximab and adalimumab in a patient with Crohn's disease.

A 61 year old woman with active luminal Crohn's disease was successfully treated with infliximab induction therapy followed by 5 infusions every 8 weeks. However, symptoms returned in the weeks preceding the 7th and 8th infusions. The 9th infusion was therefore given only 4 weeks after the 8th infusion, but an acute severe anaphylactoid reaction occurred immediately after start of the infusion.

Cut-off levels and diagnostic accuracy of infliximab trough levels and anti-infliximab antibodies in Crohn's disease.

Introduction: Reasons for infliximab failure in Crohn's disease and ulcerative colitis are debated. Serum levels of infliximab and anti-infliximab antibodies have been associated with loss of response. We aimed at determining cut-off levels for infliximab and anti-infliximab antibody concentrations associated with clinical response to infliximab maintenance therapy.

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.

[Monitoring of bioavailability, pharmacokinetics and immunogenicity of tumour necrosis factor-alpha inhibitors].

Treatment of inflammatory bowel disease (IBD) with antibodies against tumour necrosis factor-alpha (TNF) is effective. Not all patients respond, however, and the effect wears off in a considerable fraction of initial responders over time. Individual differences in bioavailability, pharmacokinetics and immunogenicity are now recognized as essential problems in the use of biologicals, and blood measurements of functional anti-TNF antibodies and antibodies against anti-TNF drugs with robust and clinically relevant methods may optimize treatment of IBD through individualized therapeutic regimens.

World Gastroenterology Organization Practice Guidelines for the diagnosis and management of IBD in 2010.

Inflammatory bowel disease (IBD) represents a group of idiopathic, chronic, inflammatory intestinal conditions. Its two main disease categories are: Crohn's disease (CD) and ulcerative colitis (UC), which feature both overlapping and distinct clinical and pathological features. While these diseases have, in the past, been most evident in the developed world, their prevalence in the developing world has been gradually increasing in recent decades.

A maximum likelihood estimator of a Markov model for disease activity in Crohn's disease and ulcerative colitis for annually aggregated partial observations.

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases that have a remitting, relapsing nature. During relapse, they are treated with drugs and surgery. The present study was based on individual data from patients diagnosed with CD or UC at Herlev University Hospital, Copenhagen, Denmark, during 1991 to 1993.

Diagnosis and management of fistulizing Crohn's disease.

The transmural inflammation characteristic of Crohn's disease predisposes patients to the formation of fistulas. Up to 50% of patients with Crohn's disease are affected by fistulas, which is a major problem given the considerable morbidity associated with this complication. Appropriate treatment of fistulas requires knowledge of specific pharmacological and surgical therapies.