The fibroid phenotype of biological naïve patients with rheumatoid arthritis are less likely to respond to anti-IL-6R treatment

Sci Rep. 2024 May 10;14(1):10751. doi: 10.1038/s41598-024-61435-2.

Abstract

Type III collagen gene expression is upregulated in the synovium of patients with rheumatoid arthritis (RA) presenting the fibroid phenotype. The soluble type III collagen formation biomarker, PRO-C3, is known to measure fibrogenesis in fibrotic diseases. In this exploratory study, we aimed to investigate the association between fibrogenesis (PRO-C3) and the disease- and treatment response in patients with RA. We measured PRO-C3 in subsets of two clinical trials assessing the effect of the anti-interleukin-6 (IL-6) receptor treatment tocilizumab (TCZ) as monotherapy or polytherapy with methotrexate. PRO-C3 levels had weak or very weak correlations with the clinical parameters (Spearman's). However, when the patients were divided into Disease Activity Score-28 groups characterized by the erythrocyte sedimentation rate (DAS28-ESR), there was a statistical difference between the PRO-C3 levels of the different groups (p < 0.05). To determine the response in relation to PRO-C3, a cut-off based on PRO-C3 levels and patients in remission (DAS28-ESR ≤ 2.6) was identified. This showed that a reduction in PRO-C3 after treatment initiation was associated with decreased DAS28-ESR and a higher response rate in patients with low PRO-C3 levels than in those with high PRO-C3 levels. This indicates that a fibrotic component affects the responsiveness of patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antirheumatic Agents* / therapeutic use
  • Arthritis, Rheumatoid* / drug therapy
  • Arthritis, Rheumatoid* / metabolism
  • Arthritis, Rheumatoid* / pathology
  • Biomarkers
  • Female
  • Humans
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Phenotype
  • Receptors, Interleukin-6* / antagonists & inhibitors
  • Receptors, Interleukin-6* / metabolism
  • Treatment Outcome

Substances

  • Receptors, Interleukin-6
  • tocilizumab
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Methotrexate
  • Biomarkers