Humoral factors in serum as predictors of therapeutic response to tumor necrosis factor inhibitors in rheumatoid arthritis

Int J Rheum Dis. 2024 Nov;27(11):e15413. doi: 10.1111/1756-185X.15413.

Abstract

Aim: This study aimed to evaluate the predictive value of serum humoral factors in determining the therapeutic responses to biologic DMARDs (bDMARDs), especially TNF inhibitors (TNFis), in patients with RA.

Methods: A cohort of 52 patients with RA who were treated with bDMARDs, including TNFis, abatacept, and tocilizumab, was analyzed. Serum samples were collected at baseline (t1), 5 ± 1 (t2), and 14 ± 2 weeks (t3) after treatment. A bead-based immunoassay was used to quantify serum cytokines/chemokines. Treatment response was determined 1 year after initiation.

Results: Distinct patterns of IL-6 behaviors were observed among different bDMARDs. Patients exhibiting IL-6 rebound at 14 weeks were more likely to be non-responders to TNFi after 1 year, and this rebound appeared to be associated with increases in IFN-γ and IL-12 levels. IFN-β was more detectable than IFN-α2 in RA. Additionally, patients with measurable IFN-β at baseline tended to be TNFi responders.

Conclusion: Monitoring serum humoral factors may offer valuable insights into the likelihood of therapeutic success of TNFi in patients with RA. IL-6 rebound at 14 weeks might serve as an early indicator of non-responsiveness to TNFi. These findings highlight the potential of personalized treatment strategies for RA based on serum humoral factor profiling. Larger prospective studies are needed to validate these results and elucidate the underlying mechanisms.

Keywords: Interleukin‐6; interferons; rheumatoid arthritis; tumor necrosis factor inhibitors.

MeSH terms

  • Abatacept / therapeutic use
  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents* / therapeutic use
  • Arthritis, Rheumatoid* / blood
  • Arthritis, Rheumatoid* / diagnosis
  • Arthritis, Rheumatoid* / drug therapy
  • Arthritis, Rheumatoid* / immunology
  • Biological Products / therapeutic use
  • Biomarkers / blood
  • Cytokines / blood
  • Female
  • Humans
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Time Factors
  • Treatment Outcome
  • Tumor Necrosis Factor Inhibitors / therapeutic use

Substances

  • Antirheumatic Agents
  • Biomarkers
  • Tumor Necrosis Factor Inhibitors
  • Interleukin-6
  • Cytokines
  • tocilizumab
  • Abatacept
  • IL6 protein, human
  • Biological Products
  • Antibodies, Monoclonal, Humanized