# Threshold Effect of C‐Reactive Protein‐Albumin‐Lymphocyte (CALLY) Index on Disease Activity in Rheumatoid Arthritis: Unveiling a Nonlinear Association

## TL;DR

This study finds a nonlinear relationship between a new biomarker (CALLY index) and disease activity in rheumatoid arthritis, suggesting it could help assess inflammation and severity.

## Contribution

The study introduces the CALLY index as a novel composite biomarker with a nonlinear association to rheumatoid arthritis disease activity.

## Key findings

- The CALLY index shows a significant negative correlation with disease activity scores in rheumatoid arthritis.
- A nonlinear relationship exists, with a threshold effect observed at specific CALLY index values.
- The negative impact of the CALLY index on disease activity weakens after a certain threshold but remains statistically significant.

## Abstract

The relationship between the C‐reactive protein (CRP)‐albumin‐lymphocyte (CALLY) index and disease activity of rheumatoid arthritis (RA) has not been explored at present. This study included 1058 RA patients and used a multiple linear regression model to evaluate the association between the CALLY index and 28 joint disease activity scores (DAS28) and further explored its potential nonlinear relationship using a two‐stage segmented linear regression model. Multivariate adjusted analysis showed that CALLY was significantly negatively correlated with DAS28‐erythrocyte sedimentation rate (ESR) (β = −0.119, 95% confidence interval [CI]: −0.145 to −0.093) and DAS28‐CRP (β = −0.201, 95% CI: −0.226 to −0.177) (both p  < 0.001), and there was a dose–response relationship (trend p  < 0.001). Segmented regression analysis revealed a significant nonlinear correlation between the two, with inflection points of 0.499 and 0.555, respectively. Below the inflection point, CALLY has a significant negative impact on disease activity (DAS28‐ESR: β = −2.102, 95% CI: −2.498 to −1.706); DAS28‐CRP: β = −2.311, 95% CI: −2.591 to −2.031); after exceeding the inflection point, this negative correlation effect significantly weakens but still maintains statistical significance. The results of this study indicate a significant nonlinear relationship between the CALLY index and the DAS28 score, especially at low CALLY levels. This study suggests the potential of CALLY as a novel composite biomarker reflecting the inflammatory status and disease severity of RA.