Tu1202 Correlation Between Infliximab Levels (IFX) and Antibody to Infliximab (ATI) in Pediatric Patients With Inflammatory Bowel Disease (IBD) With the Commercially Available Assay Using Electrochemilumescense

Rivera, Edgardo D Rivera; Liao, Chuanhong; Hof, Kathleen Van't; Mangatu, Thomas A.; Kahn, Stacy A.; Gokhale, Ranjana; Kirschner, Barbara S.

doi:10.1016/s0016-5085(14)62823-7

Cited by 5 publications

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“…Differences in serum biologic concentrations between ADAb-positive and -negative patients were found to be statistically significant in studies of ADA [42–44, 47–50, 53–55, 57, 58, 61] and INF [54, 57, 58, 61, 87–91, 97, 98, 105, 107, 111, 113, 114] across chronic inflammatory diseases. In the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate, a 12-month observational prospective cohort study, ADAbs against ADA were detected in 31 of 160 (19%) ADA-treated patients and were significantly associated with lower ADA concentrations ( r s = −0.51; p < 0.0001) [44].…”

Section: Resultsmentioning

confidence: 99%

“…In published studies of ADA [ 37 – 69 ], CZP [ 70 – 80 ], GLM [ 81 ], INF [ 1 , 2 , 36 , 45 , 46 , 54 , 57 , 58 , 60 , 61 , 63 , 64 , 67 , 82 – 117 ], RTX [ 118 ], UST [ 119 , 120 ], and CT-P13 [ 2 , 30 , 82 – 85 , 121 , 122 ], ADAb-positive patients were reported to have lower serum biologic concentrations than ADAb-negative patients. Differences in serum biologic concentrations between ADAb-positive and -negative patients were found to be statistically significant in studies of ADA [ 42 – 44 , 47 – 50 , 53 – 55 , 57 , 58 , 61 ] and INF [ 54 , 57 , 58 , 61 , 87 – 91 , 97 , 98 , 105 , 107 , 111 , 113 , 114 ] across chronic inflammatory diseases. In the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate, a 12-month observational prospective cohort study, ADAbs against ADA were detected in 31 of 160 (19%) ADA-treated patients and were significantly associated with lower ADA concentrations ( r s = −0.51; p < 0.0001) [ 44 ].…”

Section: Resultsmentioning

confidence: 99%

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Immunogenicity of Biologics in Chronic Inflammatory Diseases: A Systematic Review

et al. 2017

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ObjectivesA systematic review was conducted to explore the immunogenicity of biologic agents across inflammatory diseases and its potential impact on efficacy/safety.MethodsLiterature searches were conducted through November 2016 to identify controlled and observational studies of biologics/biosimilars administered for treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-axSpA), psoriasis (Ps), Crohn’s disease, and ulcerative colitis.ResultsOf >21,000 screened publications, 443 were included. Anti-drug antibody (ADAb) rates varied widely among biologics across diseases (and are not directly comparable because of immunoassay heterogeneity); the highest overall rates were reported with infliximab (0–83%), adalimumab (0–54%), and infliximab biosimilar CT-P13 (21–52%), and the lowest with secukinumab (0–1%), ustekinumab (1–11%), etanercept (0–13%), and golimumab (0–19%). Most ADAbs were neutralizing, except those to abatacept and etanercept. ADAb+ versus ADAb− patients had lower rates of clinical response to adalimumab (RA, PsA, JIA, AS, Ps), golimumab (RA), infliximab (RA, PsA, AS, Ps), rituximab (RA), ustekinumab (Ps), and CT-P13 (RA, AS). Higher rates of infusion-related reactions were reported in infliximab- and CT-P13-treated ADAb+ patients. Background immunosuppressives/anti-proliferatives reduced biologic immunogenicity across diseases.ConclusionsBased on reviewed reports, biologic/biosimilar immunogenicity differs among agents, with the highest rates observed with infliximab and adalimumab. As ADAb formation in biologic-/biosimilar-treated patients may increase the risk of lost response, the immunogenicity of these agents is an important (albeit not the only) consideration in the treatment decision-making process.Electronic supplementary materialThe online version of this article (doi:10.1007/s40259-017-0231-8) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Immunogenicity of Biologics in Chronic Inflammatory Diseases: A Systematic Review

et al. 2017

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“…For studies included in this review in which serum levels of biologics were reported – ADM, CZP and IFX – ADAbs-positive patients had lower serum levels of the biologic than ADAbs-negative patients ( Table 2 ). 27 – 48 …”

Section: Resultsmentioning

confidence: 99%

Immunogenicity of biologics in inflammatory bowel disease

Vermeire

Gils

Accossato

et al. 2018

Therap Adv Gastroenterol

192

146

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Crohn’s disease and ulcerative colitis are chronic inflammatory disorders of the gastrointestinal tract. Treatment options include biologic therapies; however, a proportion of patients lose response to biologics, partly due to the formation of anti-drug antibodies (ADAbs). Concomitant immunosuppressive agents reduce the development of ADAbs. This review article aims to assess the immunogenicity of biologic therapies and their clinical implications. A comprehensive literature search was conducted for articles published January 2009 to August 2015 reporting immunogenicity to adalimumab (ADM), certolizumab pegol (CZP), golimumab, infliximab (IFX), ustekinumab, and vedolizumab in inflammatory bowel disease (IBD). Eligible articles were reviewed and quality assessed by independent reviewers. Overall, 122 publications reporting 114 studies were assessed. ADAbs were reported for all agents, but the percentage of patients developing ADAbs was extremely variable, with the highest (65.3%) being for IFX administration to patients with IBD. ADAb presence was frequently associated with a reduction in primary efficacy and a loss of response, and, for IFX, an increase in adverse events (AEs). Lower serum levels of ADM, CZP and IFX were seen in ADAbs-positive rather than ADAbs-negative patients; pharmacokinetic data were unavailable for other therapies. Little information was available regarding the timing of ADAb development; studies reported their detection from as early as 10–14 days up to months after treatment initiation. Biologic therapies carry an intrinsic risk of immunogenicity, although reported rates of ADAbs vary considerably. The clinical implications of immunogenicity are a concern for effective treatment; further research, particularly into the more recently approved biologics, is required.

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“…The electronic search yielded 2558 potentially relevant articles. An additional 11 articles were identified from reference lists in review articles (19–24). After removal of duplicates, 2033 records remained, of which 1988 articles were excluded on the basis of title or abstract.…”

Section: Resultsmentioning

confidence: 99%

“…The majority of studies listed in Supplemental Table 1 (Supplemental Digital Content, http://links.lww.com/MPG/B781) used a standard dosing regimen of 5 mg/kg as established in adult trials in CD (ie, ACCENT I (5), ACCENT II (5,50), and SONIC trials (51)) or UC (ie, ACT 1 (6) and ACT 2 (52)), except for 5 studies where higher doses were used (20,26,29,32,44). One study reported on pediatric patients treated with an IFX biosimilar (41).…”

Section: Resultsmentioning

confidence: 99%

Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Infliximab in Pediatric Inflammatory Bowel Disease

Winter

Joosse

Taminiau

et al. 2020

J. pediatr. gastroenterol. nutr.

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Objectives: Infliximab (IFX), a monoclonal antibody directed against tumor necrosis factor alpha is a potent treatment option for inflammatory bowel disease (IBD). Dosing regimens in children are extrapolated from adult data using a fixed, weight-based dose, which is often not adequate. While clinical trials have focused on safety and efficacy, there is limited data on pharmacokinetic characteristics and immunogenicity of IFX in children. The objective was to provide a systematic overview of current literature on pharmacokinetic and immunogenicity of IFX in children with IBD, to assess the validity of current adult to pediatric dosing extrapolation. Methods: A literature search identified publications up to October 2018. Eligibility criteria were study population consisting of children and/or adolescents with IBD, report of IFX trough levels and/or antibodies-to IFX, full text article or abstract, article in English, and original data. Results: Initial electronic search yielded 2360 potentially relevant articles, with 1831 remaining after removal of duplicates. An additional search yielded another 202 potentially relevant articles. Of the 2033 retrieved articles, 2000 articles were excluded based on title, abstract, or eligibility criteria. Clearance of IFX was increased in young children and children with extensive disease, leading to lower trough levels after extrapolated dosing of 5 mg/kg, antibodies-to IFX emergence, and subsequent reduced efficacy. Conclusions: Adult to pediatric weight-based dosing extrapolation is often inadequate. We provide several considerations for optimal dosing of IFX in children and adolescents with IBD.

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Tu1202 Correlation Between Infliximab Levels (IFX) and Antibody to Infliximab (ATI) in Pediatric Patients With Inflammatory Bowel Disease (IBD) With the Commercially Available Assay Using Electrochemilumescense

Cited by 5 publications

References 0 publications

Immunogenicity of Biologics in Chronic Inflammatory Diseases: A Systematic Review

Immunogenicity of Biologics in Chronic Inflammatory Diseases: A Systematic Review

Immunogenicity of biologics in inflammatory bowel disease

Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Infliximab in Pediatric Inflammatory Bowel Disease

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