Utility of serum TNF-α, infliximab trough level, and antibody titers in inflammatory bowel disease

Pallagi-Kunstár, É.; Farkas, Klaudia; Szepes, Zoltán; Nagy, Ferenc; Szűcs, Mónika; Kui, Róbert; Gyulai, Rolland; Bálint, Anita; Wittmann, Tibor; Molnár, Tamás

doi:10.3748/wjg.v20.i17.5031

Cited by 32 publications

(14 citation statements)

References 16 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%

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%

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

184

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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“…Pharmacokinetic and/or clinical outcomes (efficacy and/or safety) in ADA‐positive patients were reported in 42 and 40% of adalimumab and infliximab studies, respectively. In 15 of 38 (39%) adalimumab studies and 18 of 62 (29%) infliximab studies , ADA‐positive patients had lower serum concentrations of the biological than ADA‐negative patients. The association between biological serum concentrations and ADA formation was evident in inflammatory disease states and immunoassay formats.…”

Section: Resultsmentioning

confidence: 99%

“…The association between biological serum concentrations and ADA formation was evident in inflammatory disease states and immunoassay formats. Differences in serum concentrations between ADA‐positive and ‐negative patients were found to be statistically significant in nine of 38 (24%) adalimumab studies and 12 of 62 (19%) infliximab studies . For example, in an observational cohort study of 115 patients with AS who received adalimumab, after 24 weeks of treatment serum levels of the biological were significantly higher in ADA‐negative patients than in ADA‐positive patients [12·7 mg/l (interquartile range = 8·2–18·0) versus 1·2 mg/l (0·0–2·0); P < 0·001] .…”

Section: Resultsmentioning

confidence: 99%

Immunoassay methods used in clinical studies for the detection of anti-drug antibodies to adalimumab and infliximab

Gorovits

Baltrukonis

Bhattacharya

et al. 2018

Clinical and Experimental Immunology

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SummaryWe examined the assay formats used to detect anti‐drug antibodies (ADA) in clinical studies of the anti‐tumour necrosis factor (TNF) monoclonal antibodies adalimumab and infliximab in chronic inflammatory disease and their potential impact on pharmacokinetic and clinical outcomes. Using findings of a recent systematic literature review of the immunogenicity of 11 biological/biosimilar agents, we conducted an ancillary qualitative review of a subset of randomized controlled trials and observational studies of the monoclonal antibodies against anti‐TNF factor adalimumab and infliximab. Among studies of adalimumab and infliximab, the immunoassay method used to detect antibodies was reported in 91 of 111 (82%) and 154 of 206 (75%) adalimumab and infliximab studies, respectively. In most adalimumab and infliximab studies, an enzyme‐linked immunosorbent assay or radioimmunoassay was used [85 of 91 (93%) and 134 of 154 (87%), respectively]. ADA incidence varied widely among assays and inflammatory diseases (adalimumab, 0–87%; infliximab, 0–79%). Pharmacokinetic and clinical outcomes were only reported for ADA‐positive patients in 38 of 91 (42%) and 61 of 154 (40%) adalimumab and infliximab studies, respectively. Regardless of assay format or biological used, ADA formation was associated with lower serum concentrations, reduced efficacy and elevated rates of infusion‐related reactions. Consistent with previous recommendations to improve interpretation of immunogenicity data for biologicals, greater consistency in reporting of assay methods and clinical consequences of ADA formation may prove useful. Additional standardization in immunogenicity testing and reporting, application of modern, robust assays that satisfy current regulatory expectations and implementation of international standards for marketed products may help to improve our understanding of the impact of immunogenicity to biologics.

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Utility of serum TNF-α, infliximab trough level, and antibody titers in inflammatory bowel disease

Abstract: On the basis of the present study, we suggest that the simultaneous measurement of serum TNF-α level, serum anti TNF-α concentration, and antibodies against anti TNF-α may further help to optimize the therapy in critical situations.

Cited by 32 publications

References 16 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

Immunoassay methods used in clinical studies for the detection of anti-drug antibodies to adalimumab and infliximab

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