# Longitudinal Comparison of Calprotectin and C-Reactive Protein in Rheumatoid Arthritis: Real-World Evidence Across Three Targeted Therapies

## TL;DR

This study compares calprotectin and CRP as biomarkers in rheumatoid arthritis patients on different therapies, finding that calprotectin performs better in some treatment groups.

## Contribution

The study provides real-world evidence on calprotectin's performance compared to CRP across three targeted RA therapies.

## Key findings

- Calprotectin and CRP both decreased significantly over time in RA patients on adalimumab, upadacitinib, or tocilizumab.
- Calprotectin outperformed CRP in predicting remission in patients on adalimumab or upadacitinib.
- Calprotectin retained good performance under IL-6 blockade, similar to CRP in the tocilizumab group.

## Abstract

Background/Objectives: Serum calprotectin is a promising biomarker of inflammation in rheumatoid arthritis (RA), yet real-world longitudinal comparisons across different targeted therapies remain limited. We aimed to evaluate the dynamics and remission-predictive ability of serum calprotectin and C-reactive protein (CRP) in RA patients treated with adalimumab, upadacitinib, or tocilizumab. Methods: In this retrospective cohort study, patients with RA initiating one of the above therapies were included. Serum calprotectin and CRP were measured at baseline, month 3, and month 6. Disease activity was assessed by DAS28 and Clinical Disease Activity Index (CDAI). Linear mixed-effects models adjusted for cumulative prednisone dose were used to assess biomarker trends over time. ROC curve analyses based on CDAI remission (≤2.8) evaluated the discriminative performance of calprotectin and CRP, stratified by treatment subgroups. Results: Sixty patients were enrolled (20 receiving tocilizumab, 20 adalimumab and 20 upadacitinib). Significant reductions in serum calprotectin, CRP, and DAS28 were observed over time (p < 0.001 for all), independent of treatment group. In the overall cohort including baseline, CRP outperformed calprotectin (AUC 0.739 vs. 0.636; p = 0.044). Among patients treated with adalimumab or upadacitinib, calprotectin significantly outperformed CRP (AUC 0.929 vs. 0.857; p = 0.049). In the tocilizumab group, both biomarkers showed similar AUCs (p = 0.888). Conclusions: Serum calprotectin declined significantly after treatment initiation and outperformed CRP in identifying remission under TNFα and JAK inhibition. It also retained a good performance under IL-6 blockade. These findings support its role as a treatment-sensitive biomarker suggesting a complementary role alongside CRP in RA monitoring, particularly in settings where CRP reliability is pharmacologically suppressed.