The impact of infliximab infusion reactions on long‐term outcomes in patients with Crohn’s disease

Moss, Alan C.; Fernandez‐Becker, Nielsen; Kim, K. Jo; Cury, Dídia Bismara; Cheifetz, Adam S.

doi:10.1111/j.1365-2036.2008.03734.x

Cited by 37 publications

(32 citation statements)

References 22 publications

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“…These reactions have been associated with high therapy withdrawal rates, as well as reduced remission rates in the subsequent 2 years [Moss et al 2008]. ADA and certolizumab are not administered by infusion and are therefore not associated with these reactions.…”

Section: Impact Of Antitumor Necrosis Factor α Antibody Formation On mentioning

confidence: 99%

Comprehensive review: antitumor necrosis factor agents in inflammatory bowel disease and factors implicated in treatment response

Lichtenstein

2013

Therap Adv Gastroenterol

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Antitumor necrosis factor α (anti-TNF) agents have dramatically influenced management of refractory inflammatory bowel disease (IBD). However, not all patients respond to treatment and some lose response or become intolerant over time. Immunogenicity, a well established phenomenon with anti-TNF agents, may have important clinical implications in patients with IBD. A comprehensive review of available evidence demonstrating how drug concentrations, immunogenicity, and other factors influence outcomes with anti-TNF agents was performed. PubMed, EMBASE, Biosis, Dialog, and Conference Papers Index were searched from 1 January 1995 to 7 April 2012 to identify clinical trials in adult and pediatric patients with IBD treated with anti-TNF agents for Crohn's disease or ulcerative colitis. Data on serum drug levels and immunogenicity and their relationship with clinical efficacy and safety outcomes were extracted and examined. Serum infliximab concentrations correlated with clinical efficacy and treatment outcomes in patients with IBD; this relationship is less well characterized with adalimumab and certolizumab pegol concentrations. In multiple studies, the presence and level of antibodies to infliximab correlated with loss of clinical efficacy and increased risk of infusion reactions. The incidence and clinical impact of antibody formation with adalimumab or certolizumab in IBD is becoming evident as more data become available. Current, enzyme-linked immunosorbent assay based anti-TNF antibody assays are suboptimal in that results are often inconclusive and comparisons between agents cannot be made. Measurement of anti-TNF agent drug concentrations and assessment of immunogenicity has the potential to positively impact clinical decision making during anti-TNF therapy for IBD. As assays are optimized, it is expected that the clinical impact of these determinations will be better characterized.

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Section: Impact Of Antitumor Necrosis Factor α Antibody Formation On mentioning

confidence: 99%

Comprehensive review: antitumor necrosis factor agents in inflammatory bowel disease and factors implicated in treatment response

Lichtenstein

2013

Therap Adv Gastroenterol

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“…The pathogenesis of IC-mediated infusion reactions in monkeys and humans has also been reviewed by Pavek and colleagues (1982). In humans, the role of ICs is not well understood for mAb infusion reactions but IgG ADA responses, ICs, and type 3 HSRs may contribute to serum sickness-like infusion reactions to infliximab (Baert et al 2003;Cheifetz et al 2003;Cheifetz and Mayer 2005;Colombel et al 2004;Farrell et al 2003;Hanauer et al 2004;Krishnan and Hsu 2004;Kugathasan et al 2002;Lees et al 2009;Moss et al 2008;Schutgens 2006;Seiderer, Goke, and Ochsenkuhn 2004;Svenson et al 2007;van der Laken et al 2007), rituximab (D'Arcy and Mannik 2001;Goto et al 2009;Hellerstedt and Ahmed 2003;Tamminga and Bruin 2006;Todd and Helfgott 2007), and natalizumab (Hellwig et al 2008). Such reactions can occur with non-Ig-containing therapeutic products also.…”

Section: Infusion Reactions and Generalized Type 3 Hsrsmentioning

confidence: 99%

Formation, Clearance, Deposition, Pathogenicity, and Identification of Biopharmaceutical-related Immune Complexes

et al. 2014

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Vascular inflammation, infusion reactions, glomerulopathies, and other potentially adverse effects may be observed in laboratory animals, including monkeys, on toxicity studies of therapeutic monoclonal antibodies and recombinant human protein drugs. Histopathologic and immunohistochemical (IHC) evaluation suggests these effects may be mediated by deposition of immune complexes (ICs) containing the drug, endogenous immunoglobulin, and/or complement components in the affected tissues. ICs may be observed in glomerulus, blood vessels, synovium, lung, liver, skin, eye, choroid plexus, or other tissues or bound to neutrophils, monocytes/macrophages, or platelets. IC deposition may activate complement, kinin, and/or coagulation/fibrinolytic pathways and result in a systemic proinflammatory response. IC clearance is biphasic in humans and monkeys (first from plasma to liver and/or spleen, second from liver or spleen). IC deposition/clearance is affected by IC composition, immunomodulation, and/or complement activation. Case studies are presented from toxicity study monkeys or rats and indicate IHC-IC deposition patterns similar to those predicted by experimental studies of IC-mediated reactions to heterologous protein administration to monkeys and other species. The IHC-staining patterns are consistent with findings associated with generalized and localized IC-associated pathology in humans. However, manifestations of immunogenicity in preclinical species are generally not considered predictive to humans.

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“…along the past ten years, more than 50 publications addressed to the treatment of iBD, including CD in its different forms, prove the positive results of the long and medium term therapy with the chimeric monoclonal antibody, including for infants [70][71][72][73][74][75][76][77][78] . The first promising responses for 61% of the treated patients versus 17% on placebo come from double prospective study (placebo-medicine) conducted with more than 100 patients with CD refractory to the conventional treatment, with high levels of disease activity, using different doses of infliximab (5, 10 and 20 mg/kg).…”

Section: Vol 31 Nºmentioning

confidence: 99%

Crohn's Disease: current state of biological therapy

Júnior¹

2011

J. Coloproctol. (Rio J.)

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The inflammatory bowel diseases (IBD) are defined as nonspecific chronic intestinal inflammations with possible systemic involvement. IBD have unknown etiology. The inflammatory process is complex and heterogeneous, both as to the characterization of the disease that affects the digestive tract, without an intelligible pattern of revelation and balance, and in its different systemic damages when including the extensive and severe extraintestinal symptoms. Aparently, the natural history of the disease is irregular in relation to the offending agent system and the attacked system, both in the intestinal and extraintestinal teguments. Isolated aspects showing irregularity in this balance gives us the notion that IBD, especially Crohn's disease, can be caused by the stimulation of an immune response caused by damaging agents (intestinal bacteria), but mediated by inadequate genetic factors, whose expressions determine different individual susceptibilities. These observations have been shown in genetic studies that emphasize the importance of pathological interaction between host and bacteria subsidized by a genomic region that contains genes producing proteins (NOD2 -nucleotide-binding oligomerization domain containing 2) participating in an enhanced defense response by the tissue. Increased numbers and the activation of these cells in the intestinal mucosa elevate local levels of tumor necrosis factor α (TNF-α), interleukin-1β, interferon-γ, and cytokines of the interleukin-23-Th17 pathway. So, it can be assumed that the susceptibility, which is a result of genetic alterations, is connected to an exaggerated response in the pro-inflammatory phase because of a dysfunction in the intestinal immune system. The identification of tumor necrosis factor (TNF-α) as the active element in the pro-inflammatory inadequate response gave rise to the heightened production of biological substances that could block TNF-α, at different levels, opening a large field of view to new treatment of IBD.

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The impact of infliximab infusion reactions on long‐term outcomes in patients with Crohn’s disease

Abstract: SUMMARY BackgroundLittle is known about long-term outcomes in patients who experience infusion reactions while receiving infliximab.

Cited by 37 publications

References 22 publications

Comprehensive review: antitumor necrosis factor agents in inflammatory bowel disease and factors implicated in treatment response

Comprehensive review: antitumor necrosis factor agents in inflammatory bowel disease and factors implicated in treatment response

Formation, Clearance, Deposition, Pathogenicity, and Identification of Biopharmaceutical-related Immune Complexes

Crohn's Disease: current state of biological therapy

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