Pre-treatment calprotectin (MRP8/14) provides no added value to testing CRP alone in terms of predicting response to TNF inhibitors in rheumatoid arthritis in a post-hoc analysis

Objectives
The inflammatory protein calprotectin (MRP8/14) has been identified as a promising biomarker of treatment response in rheumatoid arthritis (RA). Our aim was to test MRP8/14 as a biomarker of response to TNF-inhibitors in the largest RA cohort to date and to compare with CRP.
Methods
Serum MRP8/14 was measured in 470 RA patients about to commence treatment with adalimumab (n=196) or etanercept (n=274). Additionally, MRP8/14 was measured in the 3-month sera of 179 adalimumab treated patients. Response was determined using EULAR response criteria calculated using the traditional 4-component (4C) DAS28-CRP and alternate validated versions using 3- (3C) and 2-components (2C), CDAI improvement criteria and change in individual outcome measures. Logistic/linear regression models were fitted for response outcome.
Results
In the 3C and 2C models, RA patients were 1.92(CI:1.04-3.54) and 2.03(1.09-3.78) times more likely to be classified as EULAR responders if they had high (75th quartile) pre-treatment levels of MRP8/14 compared to low (25th quartile). No significant associations were observed for the 4C model. When only using CRP as a predictor, in the 3C and 2C analyses, patients above the 75th quartile were 3.79(CI:1.81-7.93) and 3.58(CI:1.74-7.35) times more likely to be EULAR responders and addition of MRP8/14 did not significantly improve model fit (p-value=0.62 and 0.80, respectively). No significant associations were observed in the 4C analysis. Exclusion of CRP from the outcome measure (CDAI), did not result in any significant associations with MRP8/14 (OR 1.00(CI:0.99-1.01); suggesting the associations were due to the correlation with CRP and that there is no additional utility of MRP8/14 beyond use of CRP in RA patients starting TNFi therapy.
Conclusion
Beyond correlation with CRP, we found no evidence to suggest MRP8/14 explains additional variability in response to TNFi in RA patients over and above CRP alone.