Abstract
BackgroundTocilizumab (TCZ), a humanized monoclonal antibody against the interleukin-6 receptor, has been proven to be a safe and effective treatment for rheumatoid arthritis (RA). Because RA is a heterogenous disease and patient response to treatments can vary, identifying characteristics that predict which patients are more likely to respond to TCZ is important for optimal patient care. Serum levels of C-X-C motif chemokine ligand 13 (CXCL13) and soluble intercellular adhesion molecule-1 (sICAM-1) have been associated with response to TCZ in patients with RA.ObjectivesTo evaluate the association of CXCL13 and sICAM-1 with disease activity and response to TCZ in patients with early RA and those with inadequate response to disease-modifying antirheumatic drugs (DMARD-IR).MethodsBaseline and week 24 serum CXCL13 and sICAM-1 levels were measured using available patient samples from the FUNCTION (early RA) and LITHE (DMARD-IR) trials. Correlations between CXCL13 and sICAM-1 levels and Disease Activity Score in 28 joints calculated with erythrocyte sedimentation rate (DAS28-ESR) at baseline and between change in CXCL13 and sICAM-1 and change in DAS28-ESR at week 24 were estimated. CXCL13 and sICAM-1 changes from baseline to week 24 were compared between treatment arms. The effects of TCZ treatment and baseline DAS28-ESR, CXCL13 and sICAM-1 levels on DAS28-ESR remission and 50% improvement per the American College of Rheumatology (ACR50) response at week 24 were determined.ResultsOverall, 458 patients from FUNCTION and 287 patients from LITHE were included. Correlation of baseline serum CXCL13 and sICAM-1 levels with DAS28-ESR was weak to moderate. CXCL13 and sICAM-1 levels decreased significantly at week 24 in TCZ-treated patients in both the early-RA and DMARD-IR populations. CXCL13 and sICAM-1 changes correlated moderately to weakly with DAS28-ESR changes at week 24 in both populations. The treatment regimen, but not baseline CXCL13 and sICAM-1 levels, had a significant effect on the likelihood of DAS28-ESR remission and ACR50 response.ConclusionsAlthough CXCL13 and sICAM-1 are modestly associated with RA disease activity, they do not predict response to TCZ in all RA populations.
Highlights
Rheumatoid arthritis (RA) is a pathologically heterogeneous disease, with variability between patients in the number of affected joints, antibody titers, serum cytokine levels, and severity of joint damage
C-X-C motif chemokine ligand 13 (CXCL13) and soluble intercellular adhesion molecule-1 (sICAM-1) are modestly associated with rheumatoid arthritis (RA) disease activity, they do not predict response to TCZ in all RA populations
Mean disease duration in FUNCTION was significantly shorter than in LITHE (DMARD-IR; 0.45 vs 8.65 years; P < 0.0001); mean Erythrocyte sedimentation rate (ESR) at baseline was significantly higher in patients in FUNCTION than in those in LITHE (Table 1)
Summary
Rheumatoid arthritis (RA) is a pathologically heterogeneous disease, with variability between patients in the number of affected joints, antibody titers, serum cytokine levels, and severity of joint damage. Histological and molecular heterogeneity in synovial tissue of patients with RA has been demonstrated [1,2,3]. Genome-wide expression analysis of synovial tissues from a large RA cohort demonstrated distinct molecular and cellular phenotypes, which reflect the heterogeneity present in the RA synovium [4]. Synovial tissue is often unavailable before the initiation of treatment; the use of serum biomarkers to predict which patients will respond to a specific treatment is an area of interest for rheumatologists. Because RA is a heterogenous disease and patient response to treatments can vary, identifying characteristics that predict which patients are more likely to respond to TCZ is important for optimal patient care. Serum levels of C-X-C motif chemokine ligand 13 (CXCL13) and soluble intercellular adhesion molecule-1 (sICAM-1) have been associated with response to TCZ in patients with RA
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