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Ex vivo inhibited cytokine profiling may explain inferior treatment response to golimumab after adalimumab failure in rheumatoid arthritis

1, 2, 3, 4, 5, 6

  1. Department of Rheumatology, Sint Maartenskliniek, Nijmegen, the Netherlands. l.tweehuysen@maartenskliniek.nl
  2. Department of Internal Medicine and Radboud Center for Infectious Diseases, Nijmegen, the Netherlands.
  3. Department of Internal Medicine and Radboud Center for Infectious Diseases, Nijmegen, the Netherlands.
  4. Department of Rheumatology, Sint Maartenskliniek; Department of Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands.
  5. Department of Internal Medicine and Radboud Center for Infectious Diseases, Nijmegen, the Netherlands.
  6. Department of Rheumatology, Sint Maartenskliniek; Department of Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands.

CER10130 Submission on line
2018 Vol.36, N°1 - PI 0140, PF 0143
Brief Papers

Rheumatology Article

 

Abstract

OBJECTIVES:
Clinical data suggest that the response of rheumatoid arthritis patients to treatment with golimumab is much lower among those who switched from adalimumab than among those who switched from etanercept. To elucidate the mechanism behind this difference in response to sequential biologic treatment, we examined the effect of TNF inhibitors on ex vivo cytokine production profiling.
METHODS:
In a prospective cohort study, blood samples were obtained from patients before the start of a biologic. Peripheral blood mononuclear cells were pre-incubated for 1 hour with the therapeutic in vivo concentration of adalimumab, etanercept or golimumab and stimulated for 24 hours with heat killed Candida albicans or Pam3Cys. Cytokine concentrations of IL-1β, IL-6 and TNFα were determined by ELISA.
RESULTS:
Ex vivo cytokine profiling was performed in 71 patients. Golimumab, adalimumab and etanercept significantly (p<0.01) decreased Candida albicans-induced IL-1β and IL-6 production and Pam3Cys-induced IL-6 production. In contrast to etanercept, golimumab and adalimumab decreased the concentration of TNFα below the detection limit. Absolute changes in cytokine levels after inhibition by golimumab or adalimumab were all significantly correlated (Spearman rank rs: 0.52-0.99, p<0.001). These correlations were much lower or non-significant between etanercept and either golimumab or adalimumab.
CONCLUSIONS:
High similarity between ex vivo inhibited cytokine profiling by golimumab and adalimumab, compared to etanercept, may explain the previously found inferior treatment response to golimumab after adalimumab failure. This suggests that patients who are non-responsive to adalimumab should preferably not switch to golimumab and vice versa.

PMID: 29148425 [PubMed]

Received: 28/11/2016 - Accepted : 26/06/2017 - In Press: 18/10/2017 - Published: 06/02/2018