Hematological Indices as Biomarkers in Patients With Rheumatoid Arthritis but Normal ESR/CRP Receiving...

Evidence indicates that hematological indices, such as neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and neutrophil-to-hemoglobin and lymphocyte (NHL), are valuable for assessing disease activity in rheumatoid arthritis (RA). This study investigated their potential as biomarkers for monitoring treatment response and disease improvement in RA patients receiving biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs).

A retrospective analysis was conducted on 308 active RA patients receiving IL-6 receptor inhibitors, TNF-alpha inhibitors, cytotoxic T lymphocyte-associated antigen-4-Ig (abatacept), or Janus kinase inhibitors. Hematological indices were collected at baseline and 6 months post-treatment.

Significant reductions in NLR, SII, and NHL were observed after initiation of b/tsDMARD therapy. These changes correlated with improvements in DAS28-ESR and discriminated good/moderate responders from non-responders. Each index predicted a > 1.2-point reduction in DAS28-ESR (area under the curve values ranging from 0.709 for NHL to 0.732 for SII). Adding any of these hematological indices to ESR increased sensitivity to 62.0%-63.4% versus 53.4% for ESR alone. Among patients with active disease but normal ESR/CRP, these indices (sensitivity 54.8%-66.1%) better reflected disease burden and treatment response than traditional markers (sensitivity 29.0%), which changed minimally despite DAS28-ESR improvement.

NLR, SII, and NHL are potential biomarkers for assessing treatment response in RA patients receiving b/tsDMARDs. Used alongside ESR, these indices improve evaluation of disease improvement. Notably, in clinically active patients with normal ESR/CRP levels, these indices captured treatment-related change that traditional acute-phase reactants did not, supporting their use as alternative or complementary response indicators in this setting.