Publication

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

Buurman, D. J., Blokzijl, T., Festen, E. A. M., Pham, B. T., Faber, K. N., Brouwer, E. & Dijkstra, G., 11-Dec-2018, In : PLoS ONE. 13, 12, 11 p., 0208922.

Research output: Contribution to journalArticleAcademicpeer-review

Introduction

TNF-alpha-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-alpha 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-alpha antibodies and to determine whether ATI show cross-reactivity with the IFX biosimilar CT-P13 (Inflectra).

Methods

TNF-alpha neutralization was measured using a quantitative TNF-alpha sensor assay consisting of HeLa 8D8 cells that express the Green Fluorescence Protein (GFP) under control of a NF kappa B response element. All available anti-TNF-alpha drugs and the IFX biosimilar CT-P13 (Inflectra) were tested for their TNF-alpha-neutralizing capacity. In addition, patient sera with ATI were tested for their potential to block the activity of IFX, IFX (F)ab(2)-fragment, biosimilar CT-P13 (Inflectra) and ADA.

Results

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

Conclusion

The second-generation anti-TNF-alpha drugs show increased TNF-alpha-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.

Original languageEnglish
Article number0208922
Number of pages11
JournalPLoS ONE
Volume13
Issue number12
Publication statusPublished - 11-Dec-2018

    Keywords

  • NECROSIS-FACTOR-ALPHA, CROHNS-DISEASE, CLINICAL-RESPONSE, ANTIBODIES, MAINTENANCE, ADALIMUMAB, REMISSION, TERM

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