The Bioefficacy Protocol: Biomarkers identification of TNF inhibitors efficacy in Axial Spondyloarthritis patients using transcriptome and proteome analysis

ARP Rheumatol. 2024 Oct-Dec;3(4):304-309.

Abstract

Background: Axial Spondyloarthritis (axSpA) is a chronic inflammatory rheumatic condition affecting the axial skeleton, leading to pain, stiffness, and fatigue. While biologic therapies have improved clinical management, many patients experience partial or no responses, resulting in delays in disease control. Additionally, the risk of adverse events and increased costs remains a concern.

Objectives: Our primary objectives are: 1. to identify reliable markers for treatment response to Tumor Necrosis Factor alpha inhibitors (TNFi), in particular Adalimumab, enabling the identification of individuals most likely to benefit; 2. to analyze the impact of TNFi on gene and protein expression.

Methods: A multicenter, prospective 14-week study will be conducted with 36 participants aged 18-75 years, meeting the ASAS criteria for axSpA. Patient enrollment will follow the National Guidelines for the use of TNFi in axSpA treatment, with all included patients using TNFi (Adalimumab) as a first-line option. Epidemiological and clinical data will be collected, along with peripheral blood samples, for integrated transcriptome, using RNA Seq (whole genome sequencing) and proteome analysis at various time points (baseline, 3-5 days, weeks 2 and 14), corresponding to the initial administration of TNFi. Patients will be classified as responders and non-responders, primarily based on ASAS20 criteria and secondarily based on ASDAS-C Reactive Protein (CRP), at week 14.

Discussion: This project's innovative approach lies in identifying potential biomarkers for TNFi (Adalimumab) response at baseline, paving the way for advancements in precision medicine in this field. Additionally, it seeks to establish evidence of the therapy's impact on gene and protein expression, offering deeper insights into the pathophysiological mechanisms underlying the therapeutic response.

Publication types

  • Multicenter Study

MeSH terms

  • Adalimumab* / therapeutic use
  • Adolescent
  • Adult
  • Aged
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use
  • Axial Spondyloarthritis* / drug therapy
  • Axial Spondyloarthritis* / genetics
  • Biomarkers*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Proteome*
  • Proteomics / methods
  • Transcriptome* / drug effects
  • Treatment Outcome
  • Tumor Necrosis Factor Inhibitors* / pharmacology
  • Tumor Necrosis Factor Inhibitors* / therapeutic use
  • Young Adult

Substances

  • Adalimumab
  • Tumor Necrosis Factor Inhibitors
  • Biomarkers
  • Proteome
  • Antirheumatic Agents