Background/Purpose: The biomarkers CXCL13 and sICAM1 have been associated with outcomes in patients with RA treated with TCZ. This study evaluated the association of CXCL13 and sICAM1 with disease activity and response to TCZ in early RA and DMARD-IR patients.

Methods: Patient subsets from the FUNCTION (early RA) and LITHE (DMARD-IR) clinical trials were selected based on baseline and Week 24 sample availability; serum CXCL13 and sICAM1 levels were measured. Correlations between CXCL13 and sICAM1 levels and DAS28-ESR at baseline, and between change in CXCL13 and sICAM1 levels and change in DAS28-ESR at Week 24, were determined. Changes in CXCL13 and sICAM1 levels from baseline to Week 24 were compared between treatment arms using Welch t test. The effect of treatment, baseline DAS28-ESR and baseline CXCL13 and sICAM1 levels on the likelihood of DAS28-ESR remission and ACR50 response at Week 24 was determined via logistic regression. DAS28-ESR remission and ACR50 rates were compared against CXCL13 and sICAM1 status (high vs low median values) within each trial arm using a Cochran-Mantel-Haenszel test.

Results: Overall, 458 of 872 patients from FUNCTION (TCZ + MTX, n = 160; TCZ monotherapy [TCZ-mono], n = 157; placebo [PBO] + MTX, n = 141) and 287 of 791 patients from LITHE (TCZ + MTX, n = 137; PBO + MTX, n = 150) were included. In these patient subsets, mean disease duration in FUNCTION was significantly shorter than in LITHE (0.45 vs 8.65 years). At baseline, correlation of serum CXCL13 levels with DAS28-ESR was moderate in the early RA population and weak in the DMARD-IR population (Table). Correlation between baseline serum sICAM1 levels and DAS28-ESR was low in both populations. Serum levels of CXCL13 decreased significantly at Week 24 in all treatment arms in both populations; sICAM1 levels decreased significantly at Week 24 in the TCZ-mono arm in patients with early RA and the TCZ + MTX arms in both populations but not in the PBO + MTX arms. Change in CXCL13 levels correlated moderately with change in DAS28-ESR at Week 24 in both populations (Table). Change in sICAM1 levels correlated moderately with change in DAS28-ESR at Week 24 in the DMARD-IR population but weakly in the early RA population. Although the treatment arm had a significant effect on the likelihood of DAS28-ESR remission and achievement of ACR50, the effect of baseline levels of CXCL13 and sICAM1 were not significant. DAS28-ESR remission and ACR50 response rates at Week 24 within each treatment arm of the early RA and DMARD-IR populations were not significantly different between patients with high vs low baseline CXCL13 and sICAM1 levels.

Conclusion: The association of baseline CXCL13 levels with RA disease activity was stronger in the early RA population than in the DMARD-IR population. Baseline levels of CXCL13 and sICAM1 did not predict response to TCZ at Week 24, suggesting that although these biomarkers are associated with disease activity, they do not predict response to TCZ in all RA populations.