Dataset Information

Quantitative comparison of the neutralizing capacity, immunogenicity and cross-reactivity of anti-TNF-? biologicals and an Infliximab-biosimilar.

ABSTRACT:

Introduction

TNF-?-neutralizing antibodies, such as infliximab (IFX) and adalimumab (ADA), are effective in the treatment of inflammatory bowel diseases (IBD), but they are expensive and become ineffective when patients develop anti-IFX or anti-ADA antibodies (ATI and ATA, respectively). Second-generation anti-TNF-? antibodies, such as Golimumab, Etanercept, Certolizumab-pegol and IFX biosimilars, may solve these issues.

Aim

To determine the neutralizing capacity of first- and second generation anti-TNF-? antibodies and to determine whether ATI show cross-reactivity with the IFX biosimilar CT-P13 (Inflectra).

Methods

TNF-? neutralization was measured using a quantitative TNF-? sensor assay consisting of HeLa 8D8 cells that express the Green Fluorescence Protein (GFP) under control of a NF-?B response element. All available anti-TNF-? drugs and the IFX biosimilar CT-P13 (Inflectra) were tested for their TNF-?-neutralizing capacity. In addition, patient sera with ATI were tested for their potential to block the activity of IFX, IFX (F)ab2-fragment, biosimilar CT-P13 (Inflectra) and ADA.

Results

TNF-? strongly induced GFP expression in Hela 8D8 cells. Higher concentrations of first-generation anti-TNF-? drugs were required to neutralize TNF-? compared to the second-generation anti-TNF-? drugs. Serum of IBD patients with proven ATI blocked TNF-?-neutralizing properties of IFX biosimilar CT-P13 (Inflectra), whereas such sera did not block the effect of ADA.

Conclusion

The second-generation anti-TNF-? drugs show increased TNF-?-neutralizing potential compared to first-generation variants. ATI show cross-reactivity toward IFX biosimilar CT-P13 (Inflectra), consequently patients with ATI are unlikely to benefit from treatment with this IFX biosimilar.

SUBMITTER: Buurman DJ

PROVIDER: S-EPMC6289430 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Quantitative comparison of the neutralizing capacity, immunogenicity and cross-reactivity of anti-TNF-α biologicals and an Infliximab-biosimilar.

Buurman D J DJ Blokzijl T T Festen E A M EAM Pham B T BT Faber K N KN Brouwer E E Dijkstra G G

PloS one 20181211 12

<h4>Introduction</h4>TNF-α-neutralizing antibodies, such as infliximab (IFX) and adalimumab (ADA), are effective in the treatment of inflammatory bowel diseases (IBD), but they are expensive and become ineffective when patients develop anti-IFX or anti-ADA antibodies (ATI and ATA, respectively). Second-generation anti-TNF-α antibodies, such as Golimumab, Etanercept, Certolizumab-pegol and IFX biosimilars, may solve these issues.<h4>Aim</h4>To determine the neutralizing capacity of first- and sec ...[more]

PMID: 30533022

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