Comparative Immunogenicity of TNF Inhibitors: Impact on Clinical Efficacy and Tolerability in the Management of Autoimmune Diseases. A Systematic Review and Meta-Analysis

Thomas, Sarah S.; Borazan, Nabeel; Barroso, Nashla; Duan, Lewei; Taroumian, Sara; Kretzmann, Benjamin; Bardales, Ricardo H.; Elashoff, David; Vangala, Sitaram; Fürst, Daniel E.

doi:10.1007/s40259-015-0134-5

Cited by 171 publications

(148 citation statements)

References 78 publications

(102 reference statements)

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“…The lower anti-infliximab antibodies prevalence in RA patients with methotrexate than in those without methotrexate was previously reported. 33 Nevertheless, we conducted our study only in patients without detected antiinfliximab antibodies. Our results consequently suggest an influence of methotrexate on infliximab pharmacokinetics, independent of ADA influence.…”

Section: Discussionmentioning

confidence: 99%

The underlying inflammatory chronic disease influences infliximab pharmacokinetics

Passot

Mulleman

Bejan-Angoulvant

et al. 2016

mAbs

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Infliximab is an anti-tumor necrosis factor monoclonal antibody approved in chronic inflammatory diseases such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn's disease (CD) and ulcerative colitis (UC). Infliximab pharmacokinetics is variable between patients, but influence of the underlying disease was never assessed. This study aimed at assessing this influence using a cohort of patients monitored in a single center and with the same assay. Infliximab trough concentrations were determined on samples collected between weeks 0 and 22 after treatment initiation in 218 patients treated for RA, PsA, AS, CD or UC. Infliximab pharmacokinetics was analyzed by a onecompartment population model with first-order elimination rate constant. In AS patients, volume of distribution (V) and elimination clearance (CL) were 5.4 L and 0.24 L/day, respectively. In CD and UC patients, V was 49% and 52% higher than in AS, respectively, and CL was 47% and 60% higher than in AS, respectively. In RA patients, CL was 49% higher than in AS patients. Simulations showed that without methotrexate, a 3 mg/kg dosing regimen would lead only 16% of RA patients to reach the target concentration (2.5 mg/L) at week 22, whereas target concentrations would be reached in approximately half of RA patients cotreated with methotrexate, as well as half of CD (3.5 mg/L) and UC (3.7 mg/L) patients. The suboptimality of approved dosing regimens supports the development of dosing optimization based on concentration measurements.

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Section: Discussionmentioning

confidence: 99%

The underlying inflammatory chronic disease influences infliximab pharmacokinetics

Passot

Mulleman

Bejan-Angoulvant

et al. 2016

mAbs

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“…Most TNF inhibitors are administered through repeated subcutaneous injections (with the exception of infliximab given intravenously), which is similar to the delivery of immunogenic vaccines. Of interest, combination therapy using TNF antagonists and immunosuppressive drugs such as methotrexate often decreases the incidence of antibody formation and enhances clinical efficacy (29,30 ). However, because of risks commonly associated with long-term immunosuppressive therapy, an individualized approach based on risk-benefit evaluation is preferred (31 ).…”

Section: Immunogenicity To Tnf Antagonistsmentioning

confidence: 99%

“…According to a recent comprehensive review, 25.3% of all patients treated with infliximab developed ADAs (30 ). Adalimumab, a fully human antibody, was shown to elicit antibody response in 14.1% of patients in a combined cohort of RA, spondyloarthritis, and IBD (32 ).…”

Section: Ada Responsementioning

confidence: 99%

Immunogenicity Assessment of Tumor Necrosis Factor Antagonists in the Clinical Laboratory

Lázár‐Molnár

Delgado

2016

Clinical Chemistry

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BACKGROUND Tumor necrosis factor (TNF) antagonists are increasingly used for the treatment of inflammatory and autoimmune diseases. Immunogenicity of these drugs poses therapeutic challenges such as therapeutic failure and adverse effects in a number of patients. Evaluation of clinical nonresponsiveness includes laboratory testing for drug concentrations and detecting the presence of antidrug antibodies. CONTENT This review provides an overview of the immunogenicity of TNF antagonists and testing methodologies currently available for measuring antidrug antibody response, which decreases treatment efficacy and may result in therapeutic failure. This review summarizes methodologies such as binding assays, including ELISA and HPLC-based homogenous mobility shift assay, as well as functional cell-based assays such as reporter gene assay. Furthermore, based on the laboratory findings of testing for antidrug antibody response, as well as serum drug concentrations, an algorithm is provided for interpretation, based on the current available literature and guidelines, which may aid in determining optimal therapy after treatment failure. SUMMARY Laboratory testing methodologies for measuring serum concentrations of TNF inhibitors and antidrug antibodies are clinically available. These methods provide an evidence-based, personalized approach for the workup of patients showing treatment failure, which saves time and resources, and contributes to improved patient care.

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“…Jóllehet, az anti-TNF-α hatóanyag elleni antitestkép-ződést nem lehet teljes mértékben elkerülni, mégis nyilvánvaló, hogy a teljesen humán szerkezet miatt az ADA kevésbé immunogén, mint az IFX [12]. Ezért bír nagy jelentőséggel az ADA-kezelés hatékonyságának tanulmányozása azoknál a betegeknél, akik korábban az IFXkezelésre jól reagáltak, viszont a kezelés ideje alatt intolerancia alakult ki a szerrel szemben vagy hatásvesztés következett be.…”

Section: áBraunclassified

Az adalimumab hatékonysága és biztonságossága hagyományos kezelésre refrakter colitis ulcerosában

et al. 2016

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Bevezetés: Európában 2012 óta engedélyezett adalimumab alkalmazása terápiarefrakter colitis ulcerosa kezelésére. Célkitűzés: A szerzők célja volt, hogy colitis ulcerosás betegek körében országos szinten felmérjék az adalimumab hatásosságát és biztonságosságát. Módszer: Prospektív tanulmányban felmérték a tartós klinikai válasz, a teljes remiszszió, illetve elsődleges vagy másodlagos hatásvesztés arányát a kezelés 12., 30. és 52. hetében. Értékelték az 52. héten a nyálkahártya-gyógyulás megoszlását. Eredmények: A vizsgálatba 73 aktív colitis ulcerosás beteget vontak be. Rövid távú klinikai válasz a betegek 75,3%-ában alakult ki a 12. hétre. Az adalimumabkezelés fenntarthatóságának valószí-nűsége az 52. hétig 48,6% volt, amelyet tartós klinikai válasz kísért a betegek 92%-ánál. Nyálkahártya-gyógyulás a betegek 48,1%-ában volt kimutatható az 52. héten. A betegek 17,6%-ánál terápiamódosításra, 5,4%-ánál colectomia elvégzésére került sor az egyéves időszak alatt. Következtetések: A colitis ulcerosa a kezdetektől hatékony kezelést igényel, ezzel megelőzve a szövődményeket. Az eredmények alapján az adalimumab kedvező rövid és hosszú távú hatást mutat colitis ulcerosás betegeknél. Orv. Hetil., 2016, 157(18), 706-711. Kulcsszavak: adalimumab, colitis ulcerosa, folyamatos klinikai válaszLong-term adalimumab therapy in ulcerative colitis in clinical practice: result of the Hungarian multicenter prospective study Introduction: Adalimumab was approved for the treatment of ulcerative colitis refractory to conventional therapy several years later than infliximab in Europe. Due to the relatively low remission rate observed in Ultra trials, data on the efficacy of adalimumab in ulcerative colitis are really helpful in the daily practice. Aim: The aim of this study was to prospectively collect data on induction and maintenance adalimumab therapy in patients with ulcerative colitis treated in Hungarian centres. Method: This prospective study collected data of all patients with ulcerative colitis treated with adalimumab in 10 Hungarian centres. The primary endpoints of the study were rates of remission, response and primary failure at week 12, and the rate of continuous clinical response, remission and loss of response at weeks 30, and 52. Secondary endpoints were endoscopic outcome at week 52 and comparison of the efficacy of

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Comparative Immunogenicity of TNF Inhibitors: Impact on Clinical Efficacy and Tolerability in the Management of Autoimmune Diseases. A Systematic Review and Meta-Analysis

Cited by 171 publications

References 78 publications

The underlying inflammatory chronic disease influences infliximab pharmacokinetics

The underlying inflammatory chronic disease influences infliximab pharmacokinetics

Immunogenicity Assessment of Tumor Necrosis Factor Antagonists in the Clinical Laboratory

Az adalimumab hatékonysága és biztonságossága hagyományos kezelésre refrakter colitis ulcerosában

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