Loss of Response to Anti-TNFs: Definition, Epidemiology, and Management

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Tumor necrosis factor-α (TNFα) antagonists have advanced the management of inflammatory bowel diseases patients leading to an improvement of patient's quality of life with the reduction of number of surgeries and hospitalizations. Despite these advances, many patients do not respond to the induction therapy (primary non-response—PNR) or lose response during the treatment (secondary loss of response—LOR). In this paper we will provide an overview of the definition, epidemiology and risk factors for PNR and LOR, as well as discuss the therapeutic options for managing LOR.

Related collections

Most cited references 43

Record: found
Abstract: found
Article: not found

Infliximab for induction and maintenance therapy for ulcerative colitis.

Paul Rutgeerts, William J Sandborn, Brian Feagan … (2005)

Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor alpha, is an established treatment for Crohn's disease but not ulcerative colitis. Two randomized, double-blind, placebo-controlled studies--the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively)--evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2. In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P<0.001 for both comparisons with placebo). A response was defined as a decrease in the Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute rectal-bleeding subscore of 0 or 1. In ACT 2, 64 percent of patients who received 5 mg of infliximab and 69 percent of those who received 10 mg had a clinical response at week 8, as compared with 29 percent of those who received placebo (P<0.001 for both comparisons with placebo). In both studies, patients who received infliximab were more likely to have a clinical response at week 30 (P< or =0.002 for all comparisons). In ACT 1, more patients who received 5 mg or 10 mg of infliximab had a clinical response at week 54 (45 percent and 44 percent, respectively) than did those who received placebo (20 percent, P<0.001 for both comparisons). Patients with moderate-to-severe active ulcerative colitis treated with infliximab at weeks 0, 2, and 6 and every eight weeks thereafter were more likely to have a clinical response at weeks 8, 30, and 54 than were those receiving placebo. (ClinicalTrials.gov numbers, NCT00036439 and NCT00096655.) Copyright 2005 Massachusetts Medical Society.

0 comments Cited 914 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial.

Jean-Frédéric Colombel, William J Sandborn, Paul Rutgeerts … (2007)

This study evaluated the efficacy and safety of adalimumab, a fully human, anti-tumor necrosis factor monoclonal antibody administered subcutaneously, in the maintenance of response and remission in patients with moderate to severe Crohn's disease (CD). Patients received open-label induction therapy with adalimumab 80 mg (week 0) followed by 40 mg (week 2). At week 4, patients were stratified by response (decrease in Crohn's Disease Activity Index > or =70 points from baseline) and randomized to double-blind treatment with placebo, adalimumab 40 mg every other week (eow), or adalimumab 40 mg weekly through week 56. Co-primary end points were the percentages of randomized responders who achieved clinical remission (Crohn's Disease Activity Index score <150) at weeks 26 and 56. The percentage of randomized responders in remission was significantly greater in the adalimumab 40-mg eow and 40-mg weekly groups versus placebo at week 26 (40%, 47%, and 17%, respectively; P < .001) and week 56 (36%, 41%, and 12%, respectively; P < .001). No significant differences in efficacy between adalimumab eow and weekly were observed. More patients receiving placebo discontinued treatment because of an adverse event (13.4%) than those receiving adalimumab (6.9% and 4.7% in the 40-mg eow and 40-mg weekly groups, respectively). Among patients who responded to adalimumab, both adalimumab eow and weekly were significantly more effective than placebo in maintaining remission in moderate to severe CD through 56 weeks. Adalimumab was well-tolerated, with a safety profile consistent with previous experience with the drug.

0 comments Cited 458 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Infliximab for the treatment of fistulas in patients with Crohn's disease.

D Present, P Rutgeerts, S Targan … (1999)

Enterocutaneous fistulas are a serious complication of Crohn's disease and are difficult to treat. Infliximab, a chimeric monoclonal antibody to tumor necrosis factor alpha, has recently been developed as a treatment for Crohn's disease. We conducted a randomized, multicenter, double-blind, placebo-controlled trial of infliximab for the treatment of fistulas in patients with Crohn's disease. The study included 94 adult patients who had draining abdominal or perianal fistulas of at least three months' duration as a complication of Crohn's disease. Patients were randomly assigned to receive one of three treatments: placebo (31 patients), 5 mg of infliximab per kilogram of body weight (31 patients), or 10 mg of infliximab per kilogram (32 patients); all three were to be administered intravenously at weeks 0, 2, and 6. The primary end point was a reduction of 50 percent or more from base line in the number of draining fistulas observed at two or more consecutive study visits. A secondary end point was the closure of all fistulas. Sixty-eight percent of the patients who received 5 mg of infliximab per kilogram and 56 percent of those who received 10 mg per kilogram achieved the primary end point, as compared with 26 percent of the patients in the placebo group (P=0.002 and P=0.02, respectively). In addition, 55 percent of the patients assigned to receive 5 mg of infliximab per kilogram and 38 percent of those assigned to 10 mg per kilogram had closure of all fistulas, as compared with 13 percent of the patients assigned to placebo (P=0.001 and P=0.04, respectively). The median length of time during which the fistulas remained closed was three months. More than 60 percent of patients in all the groups had adverse events. For patients treated with infliximab, the most common were headache, abscess, upper respiratory tract infection, and fatigue. Infliximab is an efficacious treatment for fistulas in patients with Crohn's disease.

0 comments Cited 399 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Clin Transl Gastroenterol

Journal ID (iso-abbrev): Clin Transl Gastroenterol

Title: Clinical and Translational Gastroenterology

Publisher: Nature Publishing Group

ISSN (Electronic): 2155-384X

Publication date (Print): January 2016

Publication date (Electronic): 07 January 2016

Publication date PMC-release: 1 January 2016

Volume: 7

Issue: 1

Page: e135

Affiliations

[1 ]The Leona M. Harry B. Helmsley Inflammatory Bowel Disease Center, The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai , New York, USA

[2 ]Meander Medical Center , Amersfoort, The Netherlands

Author notes

[* ]The Leona M. and Harry B. Helmsley Inflammatory Bowel Disease Center, The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai , One Gustave Levy Place, New York, New York 10029, USA. E-mail: jean-frederic.colombel@ 123456mssm.edu

Article

Publisher Item ID: ctg201563

DOI: 10.1038/ctg.2015.63

PMC ID: 4737871

PubMed ID: 26741065

SO-VID: 69afe76d-ad74-4aae-8cf9-b521c4cc078b

License:

Clinical and Translational Gastroenterology is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/

Loss of Response to Anti-TNFs: Definition, Epidemiology, and Management

Read this article at

Abstract

Related collections

Karger: Gastroenterology

Most cited references 43

Infliximab for induction and maintenance therapy for ulcerative colitis.

Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial.

Infliximab for the treatment of fistulas in patients with Crohn's disease.

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 255

Cited by 242

Most referenced authors 621